荔枝霜疫病的研究进展

荔枝霜疫霉(Peronophythora litchii Chen ex Ko et al)引起的荔枝霜疫病是我国荔枝生产和贮藏运输过程中为害最严重的病害,极大地威胁着我国荔枝产业的健康发展.该病可为害荔枝嫩叶、嫩枝、花穗及果实,流行年份对荔枝产量影响极大.笔者主要从荔枝霜疫病的症状、病原菌的分类和生物学特性、发生与流...     

Role of estrogen in alleviating hemorrhagic shock-induced organ injury

Estrogen has many biological activities and extensive clinical applications. Hemorrhagic shock-induced major organ dysfunction and injury, which are related to sex differences, play a triggering role in irreversible shock. The present article reviews the role of estrogen in alleviating hemorrhagic shock-induced organ injury by analyzing and summarizing the recent studies, thus expanding the clinical application of estrogen and providing a novel approach for treatment of severe hemorrhagic shock.     

科技期刊多元化若干问题浅析

科技期刊是科技信息传播交流的载体，通过各项综合性服务功能的发挥，维护着科技交流平台的稳定，并促进相关科技创新、科技产业化价值的实现，从而也实现了科技期刊自身可持续的良性发展。笔者从探讨科技期刊发展实践的角度，分析了科技期刊基于其多元化的可能性在市场经济发展实践中优化的趋势和问题。     

Key issues and research priorities in landscape ecology: An idiosyncratic synthesis

Landscape ecology has made tremendous progress in recent decades, but as a rapidly developing discipline it is faced with new problems and challenges. To identify the key issues and research priorities in landscape ecology, a special session entitled “Top 10 List for Landscape Ecology in the 21st Century” was organized at the 16th Annual Symposium of the US Regional Association of International Association of Landscape Ecology, held at Arizona State University (Tempe, Arizona, USA) during April 25–29, 2001. A group of leading landscape ecologists were invited to present their views. This paper is intended to be a synthesis, but not necessarily a consensus, of the special session. We have organized the diverse and wide-ranging perspectives into six general key issues and 10 priority research topics. The key issues are: (1) interdisciplinarity or transdisciplinarity, (2) integration between basic research and applications,(3) Conceptual and theoretical development, (4) education and training, (5)international scholarly communication and collaborations, and (6) outreach and communication with the public and decision makers. The top 10 research topics are: (1) ecological flows in landscape mosaics, (2) causes, processes, and consequences of land use and land cover change, (3) nonlinear dynamics and landscape complexity, (4) scaling, (5) methodological development, (6) relating landscape metrics to ecological processes, (7) integrating humans and their activities into landscape ecology, (8) optimization of landscape pattern, (9)landscape sustainability, and (10) data acquisition and accuracy assessment. We emphasize that, although this synthesis was based on the presentations at the“Top 10 List” session, it is not a document that has been agreed upon by each and every participant. Rather, we believe that it is reflective of the broad-scale vision of the collective as to where landscape ecology is now and where it may be going in future. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effect of atorvastatin on myocardial fibrosis induced by aldosterone

AIM: To investigate the effects and mechanisms of atorvastatin on myocardial fibrosis induced by aldosterone in SD rats. METHODS: Forty male uninephrectomized SD rats were limited to drink 1% NaCl water for 4 weeks and assigned to the follow groups: vehicle control rats (CON group); aldosterone treated rats (ALD group); spironolactone + aldosterone treated rats (SPI+ALD group); atorvastatin + aldosterone treated rats (ATO+ALD group). Blood pressure was measured by catheterization. Expression of platelet-derived growth factor (PDGF-A, PDGF-B), platelet-derived growth factor receptor (PDGFR-α, PDGFR-β) and ectodermal dysplasia-1 (ED-1) were analyzed by immunohistochemistry. Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were analyzed by Sirius-Red staining. Myocardium osteopontin protein was detected by Western blotting analysis. RESULTS: Mean arterial blood pressure in ALD group, SPI+ALD group and ATO+ALD group was elevated, and significant difference was observed between the three groups and vehicle control group (P<0.01 or P<0.05). Myocardial fibrosis was observed in ALD group. Compared to other three groups, the index of CVF and PVCA was increased significantly (P<0.01 or P<0.05). No significant difference of the index of CVF and PVCA between ATO+ALD group and SPI+ALD group was observed (P>0.05). Compared to other groups, the levels of PDGF-A, PDGF-B, PDGFR-α, ED-1 and OPN in ALD group were significantly increased (P<0.01 or P<0.05). The levels of PDGF-A, PDGF-B, PDGFR-α and OPN were no significant difference between ATO+ALD group and SPI+ALD group (P<0.01 or P<0.05). However, the level of ED-1 in ATO+ALD group was significantly decreased compared to SPI+ALD group (P<0.05). No significant difference of PDGFR-β level among four groups was found (P>0.05). CONCLUSION: These results suggest that atorvastatin may attenuate myocardial fibrosis induced by aldosterone. The mechanisms concern with reduction of macrophage infiltration, expression of inflammatory cytokines OPN, partially inhibition of platelet-derived growth factor and its receptor expression.     

Effect of aldosterone on rat peritoneal fibrosis induced by peritoneal dia-lysis

AIM: To investigate the pathologic role of aldosterone and protective effect of aldosterone receptor antagonist on peritoneal fibrosis in peritoneal dialysis rats. METHODS: A peritoneal fibrosis rat model was established by intraperitoneal injection of lipopolysaccharide(at 1 d, 3 d, 5 d and 7 d, 0.6 mg/kg) and dialysate(daily intraperitoneal injection of 4.25% dialysate, 100 mL/kg). At the same time, spironolactone(an aldosterone receptor antagonist, 100 mg·kg^-1·d^-1) was given to the model rats. After 4 weeks, the expression of aldosterone synthase CYP11B2, 11β-hydroxysteroid dehydrogenase type 2(11β-HSD2), mineralocorticoid receptor(MCR), and inflammatory factors were detected by immunohistochemistry, real-time PCR and Western blotting. RESULTS: The rat model of peritoneal fibrosis was successfully established. At the same time, the injury of mesothelial cells, deposition of collagen fibers and thickness of peritoneal were increased. Moreover, the infiltration of macrophages in the peritoneum/dialysate was increased. The level of aldosterone and the expression of MCR, 11β-HSD2 and CYP11B2 in fibrotic peritoneum were obviously up-regulated as compared with normal rats. The expression of NF-κB/MCP-1 was also increased. However, treatment with spironolactone alleviated peritoneal fibrosis and reduced the expression of NF-κB/MCP-1. CONCLUSION: Local aldosterone is involved in the process of peritoneal fibrosis via NF-κB/MCP-1 pathway. Spironolactone alleviates peritoneal fibrosis of peritoneal dialysis.     

Changes of histone modification levels in rats with liver fibrosis

AIM: To observe the changes of histone modifications in the liver of rats with hepatic fibrosis and its possible role in the development of hepatic fibrosis. METHODS: Male Wistar rats (n=20) were randomly divided into liver fibrosis group and normal control group. The liver fibrosis model was established by hypodermic injection of CCl₄, and the rats in normal control group were injected with vegetable oils. At the end of the 8th week, all rats were killed. Liver function indexes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and liver fibrosis indexes including haluronic acid (HA), laminin (LN), collagen type IV (Col Ⅳ) and procollagen type Ⅲ (PCⅢ) were determined by biochemical and RIA methods. The liver index was analyzed, and the liver fibrosis degree and the morphological change of the liver were detected by HE and Masson staining. The levels of α-smooth muscle actin (α-SMA), collagen type Ⅰ (ColⅠ), H3K4me2, H3K9me2, acH3K9 and acH4K12 were detected by Western blot. RESULTS: After hypodermic injection of CCl₄ for 8 weeks, the liver index, ALT, AST, HA, LN, Col Ⅳ and PCⅢ of the rats in liver fibrosis group were higher than those in control group (P<0.05). Compared with control group, the level of acH4K12 was decreased (P<0.05), while acH3K9, H3K9me2, α-SMA and ColⅠ were increased (P<0.05), but H3K4me2 had no significant change.CONCLUSION: The levels of acH4K12, acH3K9 and H3K9me2 may play essential roles in the pathogenesis of liver fibrosis, and these histone modifications may regulate gene expression associated with extracellular matrix metabolism.     

Role of mineralocorticoid receptor in bleomycin-induced pulmonary fibrosis

AIM:To investigate the role of mineralocorticoid receptor (MR) in the lungs of experimental fibrotic mice. METHODS:C57BL/6 male mice (6～8 weeks old) were randomly divided into control group, bleomycin treatment group (Bleo) and bleomycin+spironolactone treatment group (Bleo+Spiro). For induction of pulmonary fibrosis, the mice were administered bleomycin at dose of 2.5 mg/kg dissolved in 50 μL saline by the intratracheal route or given 50 μL sterile saline as control. The mice in Bleo+Spiro group were treated with spironolactone (20 mg/kg) daily by oral gavage throughout the experiment. The mice were sacrificed at 12 h, 1 d, 2 d, 3 d, 7 d, 14 d and 28 d after administration of bleomycin. HE staining and Masson’s trichrome staining were used to conduct histopathologic examination. The mRNA expression levels of collagen 1 (Col1), collagen 3 (Col3), transforming growth factor beta (TGF-β), monocyte chemoattractant protein 1 (MCP-1), and MR were examined by real-time PCR. RESULTS:The results of histological analysis revealed the classical pathological stages of bleomycin-induced lung fibrosis, including acute inflammation phase (from 12 h to 3 d), progressive fibrosis phase (14 d) and late fibrosis phase (28 d). Compared with Bleo group, the inflammatory responses of the lungs in Bleo+Spiro group were attenuated in the acute inflammation phase and the degree of fibrosis was significantly reduced at 14 d after administration of bleomycin. Treatment with spironolactone effectively down-regulated the mRNA expression of MR. The levels of MCP-1 (in the acute inflammation phase), TGF-β (at 14 d), Col1 and Col3 (at 14 d) were also significantly reduced. CONCLUSION: Blockage of MR significantly attenuates the degree of bleomycin-induced pulmonary fibrosis by regulating the production and secretion of MCP-1 and TGF-β, thus reducing the degree of inflammation and inhibiting the expression of TGF-β in the progressive fibrotic phase.     

Effect of bitter melon on liver fibrosis induced by carbon tetrachloride

AIM: To investigate the effects of bitter melon (BM) on liver fibrosis induced by CCl₄ in Wistar rats. METHODS: Healthy male Wistar rats were randomly divided into 4 groups (with 8 each): olive oil control group (group C), olive oil CCl₄ model group (group M), CCl₄+BM at low concentration (BM 100 g/kg, group BM-L), CCl₄+ BM at high concentration (BM 200 g/kg, group BM-H). All rats except those in group C were subcutaneously injected with CCl₄ twice a week for 8 weeks to induce liver fibrosis. After injection of CCl₄ for 8 weeks, all rats were sacrificed and the samples of blood and livers were collected. The weight ratio of liver to body was measured. The serum level of MDA and the activity of SOD were tested. The contents of total protein and albumin, the activity of GSH-Px, the content of hydroxyproline and the activity of monoamine oxidase in the liver homogenate were determined. Hepatic inflammation and collagen deposition were observed under microscope with Masson staining. RESULTS: In the rats treated with BM, the weight ratio of liver to body, the serum level of MDA, the content of hydroxyproline and the activity of monoamine oxidase in the liver homogenate were lower than those in group M (P<0.01). The serum activity of SOD, the contents of total protein and albumin, and the activity of GSH-Px in the liver homogenate were enhanced (P<0.01). The livers of the model rats had remarkable inflammatory necrosis, collagen accumulation and fibrosis. The rats in BM-treated group showed slighter hepatic injury and collagen deposition, and the liver functions were much better than those in the model group. High dose of BM showed more obvious liver-protective effects. CONCLUSION: BM attenuates liver fibrosis by its antioxidant effect and the mechanisms of reducing hydroxyproline content and monoamine oxidase activity.     

Effect of renal sympathetic denervation on cardiac hypertrophy and fibrosis

AIM:To investigate the effect of renal sympathetic denervation (RDN) on cardiac hypertrophy and fibrosis and to explore the underlying mechanisms. METHODS:Male SD rats were randomly divided into 4 groups: sham, sham plus RDN, aortic constriction (AC) and AC plus RDN group (n=15 for each group). After the intervention for 8 weeks, the haemodynamic data and cardiac function were measured by a physiological recorder. The histological structure of the heart was evaluated by HE and picro-sirius red staining. The plasma concentration of norepinephrine (NE), renin activity, angiotensin II (Ang II) concentration and cardiac Ang II level were determined by radioimmunoassay. RESULTS:Compared with AC group, RDN improved cardiac diastolic function ［left ventricular end-diastolic pressure: (8.03±1.66) mmHg vs(15.77±2.14) mmHg; -dp/dt: (7 793±587) mmHg/s vs(6 353±475) mmHg/s; both P<0.01］, inhibited cardiac hypertrophy ［left ventricular index: 3.340±0.121 vs4.244±0.102; cardiomyocyte area: (332.9±28.9) μm2 vs(401.6±33.2) μm2; both P<0.01］ and attenuated cardiac fibrosis (collagen volume fraction: 7.76%±0.85% vs12.48%±1.82%; P<0.01) in aortic constricted rats. However, RDN didn’t cause significant reduction of blood pressure in aortic constricted rats (P>0.05). RDN prevented the AC-induced increase in the plasma NE concentration, renin activity, Ang II concentration and cardiac Ang II level. CONCLUSION: RDN may directly prevent cardiac hypertrophy and fibrosis and improve cardiac function via regulating the sympathomimetic activity and renin-angiotensin system.     

Effect of imatinib on myocardial fibrosis in DOCA-salt hypertensive rats

AIM: To investigate the effects of imatinib (IMA), one of platelet-derived growth factor receptor (PDGFR) inhibitors, on myocardial fibrosis in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Sixty male uninephrectomized SD rats were treated with 1% NaCl and 0.2% KCl in the drinking water for 4 weeks and assigned to 3 groups: vehicle control group (control group), DOCA treatment group (DOCA group), DOCA and IMA treatment group (DOCA+IMA group). Systolic blood pressure (SBP) was measured using the tail-cuff method. Myocardial tissue inflammation was analyzed by hematoxylin-eosin staining. Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were analyzed by Sirius red staining. Ectodermal dysplasia-1 (ED-1) was analyzed by immunohistochemistry. Expression levels of platelet-derived growth factors (PDGF-A and PDGF-C), PDGF receptor α (PDGFRα) and phosphorylated PDGFRα (p-PDGFRα) were detected by Western blotting. RESULTS: SBP in DOCA group and DOCA+IMA group were signficantly higher than that in control group. No significant difference of SBP between DOCA group and DOCA+IM group was observed. In DOCA group, severe myocardial fibrosis was found, and CVF and PVCA were higher than those in control group. The differences of the CVF and PVCA between DOCA+IMA group and control group were detected, but the CVF and PVCA in DOCA+IMA group were significantly lower than those in DOCA group. Compared with control group, different degrees of myocardial tissue inflammation and monocyte/macrophage infiltration were observed in DOCA group and DOCA+IMA group. The expression levels of PDGF-A, PDGF-C and PDGFRα in DOCA group and DOCA+IMA group were much higher than those in control group, but the expression of p-PDGFRα in DOCA+IMA group were signficantly lower than that in DOCA group. CONCLUSION: Mineralocorticoid-induced myocardial fibrosis is related to cardiac tissue inflammatory response, excessive monocyte/macrophage infiltration and expressions of PDGF-A,PDGF-C and PDGFRα. Imatinib has an inhibitory effect on the myocardial fibrosis. The mechanisms may be associated with the inhibition of PDGFRα activity on the surface of fibroblast, thus interrupting PDGFs signaling-induced fibroblast division and proliferation.     

Expression and modulation of connective tissue growth factor in renal interstitial fibrosis

CTGF, a member of the CCN family of immediate early genes, is a recently discovered profibrotic growth factor, which is involved in many pathophysiologic procedures. CTGF acts as a downstream effector of TGF-β acting on interstitial cells to enhance the progression of fibrotic renal diseases. It has been shown that CTGF gene expression can be induced or blocked by some kinds of cytokine and drugs. It is an interesting candidate target for future intervention strategies of renal interstitial fibrosis.     

The changes in proliferation and apoptosis of macrophages in the development of pulmonary fibrosis of rats

AIM: To observe the changes in proliferation and apoptosis of macrophages in the development of pulmonary fibrosis in rats. METHODS: The number of macrophages, apoptotic cells, the proliferation index (PI) and MTT activity of macrophages were assayed on the day 14 and the day 30 after intratracheal adminstration BLMA₅ in rats. RESULTS: (1) The number of alveolar macrophages was increased in BLMA₅ 14 d group and in BLMA₅ 30 d group, compared with sham 14 d group and sham 30 d group, respectively. The number of macrophages in BLMA₅ 14 d group was higher than that in BLMA₅ 30 d group. (2) The PI of macrophages increased in BLMA₅ 14 d group, and decreased in BLMA₅ 30 d group. (3) The number of apoptotic cells increased both in BLMA₅ 14 d group and BLMA₅ 30 d group. The number of apoptotic cells in BLMA₅ 14 d group was lower than that in BLMA₅ 30 d group. (4) The MTT activity of macrophages was higher in BLMA₅ 14 d group and in BLMA₅ 30 d group than that in sham 14 d group and sham 30 d group, respectively. CONCLUSIONS: The ability of proliferation increased at first, and then decreased, but the apoptosis of macrophages increased all the time, in the development of pulmonary fibrosis. This might be partly contributed to the changes of the number and function of macrophages in lung.     

大蒜各器官的生长发育与二次生长的相关性探讨

以成蒜早4号蒜薹为材料,通过解剖测量不同时期蒜薹、蒜薹尾、二次生长、蒜头等器官的生长变化,分析各生物量的相关性.结果表明,大蒜二次生长的迅速生长呈现2个阶段,分别与蒜薹尾和蒜薹的迅速生长阶段相对应.     

Effect of Chaihushugansan on pancreatic fibrosis in mice with chronic pancreatitis induced by DBTC plus ethanol and its anti-oxidation mechanism

AIM:To explore the role of superoxide dismutase (SOD) and malondialdehyde (MDA) in chronic pancreatitis (CP) induced by dibutyltin dichloride (DBTC) combined with ethanol, and the mechanisms for prevention and treatment of pancreatic fibrosis by Chaihushugansan. METHODS:The KM mice were randomly divided into control group, CP group (DBTC combined with ethanol) and Chaihushugansan group (CP+Chaihushugansan). Except for control group, the mice in other groups were intravenously injected in tail with DBTC (8 mg/kg) and drank 10% ethanol. The mice in Chaihushugansan group were administered intragastrically with Chaihushugansan (6 g·kg-1·d-1) at the following experimenal period. Before modeling and 1 week, 2 weeks, 4 weeks and 8 weeks after modeling, the mice were anesthetized and sacrificed. The activity of amylase and the content of hyaluronic acid in the serum were measured. The morphology and the degree of fibrosis in the pancreas were observed by HE staining. The activity of SOD and the level of MDA in the pancreas homogenate were analyzed. The protein of pancreas was extracted to detect the expression of type I collagen by Western blotting. RESULTS:DBTC combined with ethanol induced CP with increased serum amylase and hyaluronic acid levels， while the serum amylase and hyaluronic acid levels in Chaihushugansan group were significantly lowered (P<0.05). In 1 week, 2 weeks, 4 weeks and 8 weeks, the pancreas were obviously injured and appeared different degrees of fibrosis. The content of MDA and the expression of type I collagen in the increased significantly, but the SOD was decreased. In Chaihushugansan group, the pathological damage and the degree of fibrosis of the pancreas were improved. The level of MDA and type I collagen expression in the pancreas were significantly reduced, but the SOD was increased. CONCLUSION: The oxidative stress may take part in the development of CP. Inhibition of oxidative stress in the pancreas is one of the mechanisms that Chaihushugansan attenuates the development of CP.     

Expression and probable role of extracellular signal-regulated protein kinases in renal fibrosis associated with diabetic in mice

AIM: To investigate the expression and probable role of extracellular signal-regulated protein kinase (ERK1/2) in renal fibrosis associated with diabetic in mice.METHODS: Male homozygous C57BL/6 mice were divided at random into control group (intraperitoneally injected with citrate buffer) and diabetes group (received 5 consecutive daily intraperitoneal injections of streptozotocin at dose of 50 mg·kg^-1·d^-1).All mice were followed up for 16 weeks.Diabetes was confirmed by serum glucose levels exceeding 16.7 mmol/L.Mice were killed at 0,4,8,12 and 16 weeks respectively after streptozotocin injection.The kidney tissues were obtained from diabetic and control mice.Serum glucose,kidney weight/body weight (KW/BW),24 h albumin excretion rate (UAE) and the serum creatinine (Scr) were measured.The kidney tissue was used for histological and morphometric studies of glomerular size,glomerular matrix expansion (PAS),and the expression of TGF-β₁,phosphorylated ERK1/2 and collagen Ⅲ by immunohistochemical staining.RESULTS: The serum level of glucose in streptozotocin -induced diabetic mice increased significantly.The kidney weight/body weight ratio,glomerular volume and glomerular matrix expansion in diabetic mice were obviously higher than those in control mice.Serum creatinine and 24 h albumin excretion rate in diabetic mice increased significantly compared with control mice.TGF-β₁,phosphorylated ERK1/2 and collagen Ⅲ levels were obviously increased in the kidney of diabetic mice compared with those in control mice (P<0.01).TGF-β₁ expression was positively related to the expression of phosphorylated ERK1/2.CONCLUSION: The overexpression of phosphorylated ERK1/2 in diabetic kidney may play an important role in the development of renal fibrosis associated with diabetic nephropathy in mice.     

Effect of resveratrol on autophagy and renal interstitial fibrosis in kidney of diabetic mice

AIMTo observe the effect of resveratrol (Res) on renal autophagy level and renal interstitial fibrosis in the mice with diabetes mellitus (DM), and to discuss the possible mechanism. METHODSThe wild-type C57BL/6 mice were randomly divided into 3 groups, including normal control (NC) group, DM group and Res group (8 in each group). The diabetic mouse model was established by injection of streptozotocin. After 8 weeks of successful replication of the diabetic model, Res was given to the mice in Res group by continuous gavage for 12 weeks, and then the mice in each group were sacrificed to detect the relevant biochemical parameters. The pathological changes of the kidney tissues were observed by HE staining and Masson staining. The levels of the proteins related to autophagy, epithelial-mesenchymal transition (EMT) and fibrosis were determined by Western blot. The mRNA expression of collagen type IV (Col IV), α-smooth muscle actin (α-SMA) and E-cadherin were detected by real-time PCR. RESULTSCompared with NC group, fasting blood glucose (FBG), kidney index (KI), serum creatinine, 24-hour urinary albumin excretion rate and 24-hour urine total protein were remarkably increased in DM group (P<0.05). The results of HE and Masson staining indicated that renal tissue presented fibrosis in DM group. The protein levels of E-cadherin, beclin-1, microtubule-associated protein 1 light chain 3-II (LC3-II) were reduced in DM group, while the levels of α-SMA, Col IV and Snail1 were increased (P<0.05). After intervention with Res for 12 weeks, all the relevant biochemical parameters and KI were reduced (P<0.05) except FBG (P>0.05), and renal fibrosis lesions were obviously alleviated. Compared with DM group, the protein levels of E-cadherin, beclin-1 and LC3-II were increased in Res group, but the protein expression levels of α-SMA, Col IV, Snail1 were reduced (P<0.05). Compared with DM group, the mRNA level of E-cadherin was increased in Res group , but the mRNA levels of Col IV and α-SMA were reduced (P<0.05). CONCLUSION Resveratrol significantly inhibits EMT and reduces renal interstitial fibrosis in diabetic mice, and its mechanism may be related to the promotion of renal autophagy.     

The augmentative effect of inducible nitric oxide synthase on pulmonary fibrosis progression

AIM: To study the up-regulation of inducible nitric oxide synthase (iNOS) in lung of pulmonary fibrosis and its relationship with fibrosis. METHODS: The changes of amount of iNOS positive stain cells and type Ⅰ?Ⅲ collagen were examined on the day 7, 14 and 30 after intratracheal administration of bleomycin A₅. The contents of NO₂^-/NO₃^- (nitrite/nitrate) in out-flowing pulmonary blood (OPB), hydroxyproline in lung and the histological changes were detected after iNOS was blocked by aminoguanidine (AG). RESULTS: (1) The number of iNOS-positive stain cells increased significantly in BLMA₅ 7 d, 14 d and 30 d groups compared with that in control group (P<0.01). Furthermore, the increment of the number of iNOS-positive stain cells in BLMA₅ 7 d, 14 d groups was more than that in BLMA₅ 30 d group. There was an increment of collagen in BLMA₅ 14 d group and in BLMA₅ 30 d group , with an increase in type Ⅲ collagen in BLMA₅ 14 d group and an increase in type Ⅰcollagen in BLMA₅ 30 d group. (2) The high level of NO₂^-/NO₃^- in OPB and hydroxyproline level in lung could be reversed by AG, a selective inhibitor of iNOS. Large amount of fibroblasts and macrophages were also abated by AG. CONCLUSION: In the development of pulmonary fibrosis, the expression of iNOS is up-regulated, which induces nitric oxide (NO) production and promotes propagation of pulmonary fibrosis.     

Comparison of in vivo anti-fibrotic effects of pirfenidone and nintedanib in bleomycin-induced pulmonary fibrosis model

AIM: To compare the effects of pirfenidone and nintedanib on bleomycin-induced mice pulmonary fibrosis model in different periods. METHODS: Five mice models were established according to the schedule of drug administration:a inflammatory phase model and 4 fibrotic phase models including the early prevention study group, early therapy study group, late therapy study group and full-course therapy study group. The indicators of lung inflammatory and lung fibrosis were detected respectively. RESULTS: (1) The level of anti-inflammatory and antioxidant indicators:both pirfenidone and nintedanib reduced the number of inflammatory cells and inhibited the secretion of inflammatory factors. Pirfenidone had a better effect on inhibition of interleukin (IL)-1β and IL-4 (P < 0.01), while nintedanib had a better effect on inhibition of IL-6 and IFN-γ (P < 0.05). Pirfenidone significantly increased superoxide dismutase (SOD) activity (P < 0.01), and nintedanib significantly reduced malondialdehyde (MDA) and myeloperoxidase (MPO) levels (P < 0.01). (2) Collagen content in lung tissue:the inhibitory effect of nintedanib on hydroxyproline content in mouse lung was better than that of pirfenidone in the early therapy study group, late therapy study group and full-course therapy study group of the fibrotic phase models (P < 0.05). Pirfenidone had a better inhibitory effect on hydroxyproline content than nintedanib in the early prevention study group (P < 0.01). (3) Pathological evaluation of lung tissue:both pirfenidone and nintedanib reduced the inflammatory infiltration and fibrotic area of the lung tissues. The inhibition trend was consistent with that of collagen content. CONCLUSION: Both pirfenidone and nintedanib have anti-inflammatory, anti-oxidative and anti-fibrosis effects in bleomycin-induced pulmonary fibrosis in mice. Pirfenidone is more effective in the early prevention study group, and nintedanib has a better effect in early therapy study group, late therapy study group and full-course therapy study group.     

The kinetic alteration of nitric oxide formation in the lungs in the development of pulmonary fibrosis of rats

AIM: To observe the kinetic alteration of nitric oxide formation in the lungs in the development of pulmonary fibrosis in the rat. METHODS: The contents of hydroxyproline in the lungs, NO₂^-/NO₃^- (nitrite/nitrate) in out-flowing and in-flowing pulmonary blood (OPB, IPB) were assayed on the day 7, 14, 21, 30 and 70 after intratracheal administration of bleomycin A₅ . The content of NO₂^-/NO₃^- in supernatants of culture of the alveolar macrophages (AMs) and the amount of iNOS positive stain cells in lung tissue section were also observed in the rat on 14th day after-bleomycin A₅ administration. RESULTS: The content of lung hydroxyproline had no change on the 7th day, increased on the 14th day (P＜0.05), increased significantly on the 21th day, 30th day and 70th day post-bleomycin A₅ compared with control rats. On the 7th day and 14th day, the content of NO^- ₂ /NO₃^- increased in OPB and decreased in IPB (P＜0.01). On the 21th day, the content of NO₂^-/NO₃^- abated in OPB (P＞0.05) but still decreased in IPB (P＜0.01). On the 30th day and the 70th day, the NO₂^-/NO₃^- level recovered both in OPB and IPB. AMs from rats on the 14th day post-bleomycin A₅ showed significant elevation (P＜0.01) in NO₂^-/NO₃^- level. The amount of iNOS positive stain cells increased in rats on the 14th day post-bleomycin A₅. CONCLUSION: The amount of NO in the lungs was high in the initial phase of fibroproliferative reaction induced by bleomycin A₅ ,and these might be associated with the enhanced ability of AMs to release NO and the increased amount of iNOS.