Effect of Yangyu Tuji on content of type Ⅰ, Ⅲ collagen and the expression of MMPs and TIMP-1 in wound caused by streptozotocin in rats

AIM: To study the effects of Yangyu Tuji (YYTJ) on delayed healing wound of diabetic rats caused by streptozotocin (STZ). METHODS: SD male rats were randomly divided into control group (control), model group (model); and 3 different dose groups of YYTJ. 55 mg/kg STZ were given by intraperitoneal injection except for control group. After 30 days, a round skin of 1.6 cm diametre was excised on all dorsal back of rats. The healing time and healing rate were observed according to re-epithelization. The content of collagenⅠ and Ⅲ was observed by Picric acid-Sirius red staining , Matrix metalloproteinase-1, 13 (MMP-1, -13), tissue inhibitor of metalloproteinases-1 (TIMP-1) by immuno-histochemistry assay. All data were analyzed by IPP software. RESULTS: The healing time in each group treated with YYTJ was shorter than that in model group (P<0.01), and the healing rate was increased (P<0.01, P<0.05). Content of type I collagen, ratio of type Ⅰ and Ⅲ collagen of high and mid dose group were significantly higher than that in model group (P<0.01) at 3rd, 7th, 11th day. The expression of MMP-1, -13 of each groups were higher than that in model group at 7th day (P<0.01, P<0.05), and MMP-1 trend to equal with model group at 11th day. MMP-13 was significantly lower than that in model group at 11th day (P<0.01, P<0.05). TIMP-1 of each group of wound was higher than that in model group at 3rd, 7th, 11th day (P<0.01, P<0.05). The ratio of type Ⅰ and Ⅲ collagens in each group was lower than that in model group at 11th day (P<0.01). Ratio of MMP-13 and TIMP-1 of high dose group and mid dose group were higher than that in model group at 3rd and 7th day (P<0.01). The ratio of each group was lower than that in model group at 11th day (P<0.01). Meanwhile, ratio of MMP-13 and TIMP-1 of high dose group and mid dose group were lower than that of lower dose group (P<0.05). CONCLUSION: It is possible that YYTJ accelerates wound healing by increasing collagen content of type Ⅰ and Ⅲ, especially type Ⅰ, as well as improves collagen deposition by regulating the balance of MMP and TIMP.     

MMP-7,MMP-10 and TIMP-4 expression in ventricular remodeling of human heart failure

AIM:To sieve matrix metalloproteinases (MMPs) and the tissue inhibitors of matrix metalloproteinases (TIMPs) closely associated with ventricular remodeling of human heart failure using antibody chip technology.METHODS:We performed cytokine-specific antibody array analysis using individual left ventricular myocardial samples from 6 patients with heart failure due to arrythmogenic right ventricular cardiomyopathy (ARVC) undergoing transplantation and matched samples from 6 non-failing subjects to screen differentially expressed MMPs and TIMPs associated with the ventricular remodeling of heart failure.The results were further validated by ELISA and immunohistochemical analysis.RESULTS:We identified high expression of MMP-7 and MMP-10 and low expression of TIMP-4 in ARVC failing hearts compared to non-failing hearts by hybridization with the cytokine-specific antibody arrays containing 17 MMPs and 4 TIMPs on the chips.ELISA and immunohistochemical analyses further confirmed that differentially expressed levels of MMP-7, MMP-10, and TIMP-4 were observed not only in ARVC failing heart, but also in failing hearts due to ischemic (ICM) and dilated cardiomyopathy (DCM).CONCLUSION:Highly expressed MMP-7 and MMP-10 and lowly expressed TIMP-4 may be involved in the ventricular remodeling of heart failure derived from cardiomyopathy of different etiology.     

Effects of angiotensionⅡon metalloproteinases and matrix in hypertrophied myocardium from infarcted rats

AIM: To investigate the roles of angiotensionⅡ (AngⅡ) receptors (AT₁, AT₂) antagonists on matrix metalloproteinases (MMPs) and extracellular matrix (ECM) system in septal myocardium from infarcted rats.METHODS: The model of rat myocardium infarction (MI) was established by permanent ligation of the left coronary artery. The treatments of the AT₁ receptor antagonist valsartan (10 mg·kg^-1·d^-1) or AT₂ receptor antagonist PD123319 (30 mg·kg^-1·d^-1) were started 7 days prior to surgery. On day 14 after MI, protein levels of MMP-2, 3, 9, fibronectin (FN), tenascin-C (TN-C) in interventricular septum (IS) were determined. The distributions of FN and TN-C were also determined by immunofluorescence.RESULTS: Pathological changes of IS on day 14 after MI showed typical myocardial hypertrophy. Protein expressions of MMP-2, 3, 9 and TN-C of IS in banding group were higher than those in sham-operation group (P<0.01). The expressions of TIMP-1 and FN were lower than those in sham-operation group (P<0.01). Protein expressions of MMP-2, 3, 9 and TN-C in valsartan group were obviously lower than those in banding and PD123319 groups (P<0.01). TIMP-1 and FN protein expressions in valsartan group were higher than those in banding and PD123319 groups (P<0.01). No difference between banding and PD123319 groups was observed (P>0.05).CONCLUSION: AngⅡis involved in myocardium remodeling in infarcted rats, which is mediated via AT₁ receptor to degrade matrix by MMPs. The heart protection of AT₁ receptor antagonists may relate to inhibition of MMPs.     

Effects of angiotensin II type 2 receptor blocker on wound healing in a mouse skin full-thickness injury model

AIM：To observe the effect of angiotensin II (Ang II) and its type 2 receptor (AT2R) on re-epithelialization, granulation tissue formation and growth factor production during wound healing, and to explore the possible mechanism by which Ang II and AT2R influence wound healing. METHODS：Two full-thickness skin wounds were created on the dorsum of C57BL/6J mice. The animals were treated with or without AT2R blocker PD123319 at a dose of 10 mg/kg daily after wounding. Specimens were taken from the wound of each mouse on days 3, 5, 7, 9, 11, 13 and 15 after wounding. Re-epithelialization and granulation tissue formation in the wounded skin tissues were evaluated by HE staining. The production of growth factors,epidermal growth factor (EGF),vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in wounded tissues during the healing process was detected by ELISA. RESULTS：Treatment with PD123319 significantly increased the rate of re-epithelialization and the area of granulation tissue compared with control group at 5 d and 7 d after wounding. Moreover, peritoneal application of PD123319 increased the production of EGF, VEGF and bFGF in the wounded tissues at the indicated time points after wounding. CONCLUSION：AT2R blocker PD123319 accelerates wound healing via promoting re-epithelialization,granulation tissue formation and growth factor production.     

Expression changes of Wnt/β-catenin signaling pathway in diabetic ulcer

AIM: To observe the effect of Wnt/β-catenin signaling pathway on diabetic ulcer. METHODS: Diabetic animal model was established in the female Wistar rats by intraperitoneal injection of low-dose streptozotocin following high-fat diet feeding. A circular wound was made on the dorsum of the rats in both control group and diabetic group. The condition of wound healing was recorded and the structures of the wound tissues were observed by HE staining in the 2 groups at 3, 7 and 14 d after wounding. The expression of β-catenin, GSK-3β and Rspo-3 at mRNA and protein levels in the wound tissues was detected by RT-PCR and ELISA. RESULTS: In diabetic group, the wound healing rate was lower (P<0.05), and the inflammatory cells, fibroblast cells and new capillaries in the wound tissues were fewer than those in control group. The expression of β-catenin and Rspo-3 at mRNA and protein levels in the wound tissues in control group was significantly higher than those in diabetic group, and the expression of GSK-3β was exactly the opposite (P<0.05). CONCLUSION: The down-regulation of Wnt/β-catenin probably resultes from the decreased level of Rspo-3, which may be one of the reasons for delaying the diabetic ulcer healing.     

Effects of arsenic trioxide on activities of MMPs and expression of TIMP-1 and TGF-β1 in skin fibroblasts and polymorphonuclear neutrophils

AIM: To observe the effects of arsenic trioxide (As₂O₃) on activities of matrix metalloproteinases (MMPs), expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor beta1 (TGF-β₁) in human fibroblast (hFb), and to discuss weather As₂O₃ promotes the healing of chronic skin ulcer through regulating collagen metabolism. METHODS: Zymography was used for testing activity of MMP-9 deriving from rat polymorphonuclear neutrophils (PMNs) and activities of MMP-1, MMP-2 secreted by hFb. Immunocytochemical method was used to determine the expressions of TIMP-1 and TGF-β₁. RESULTS: At the concentration of 50 mg/L, As₂O₃ elevated the activity of MMP-9 (P<0.01). At the concentration of 0.8 mg/L, As₂O₃ increased the activities of MMP-1 and MMP-2 (P<0.01, respectively). After hFb was cultured with As₂O₃ for 6 h, 12 h and 18 h, the expressions of TIMP-1 and TGF-β₁ decreased continuously (P<0.01). CONCLUSION: As₂O₃ elevates the activities of MMP-1, MMP -2 and MMP-9, also inhibits the expressions of TIMP-1 and TGF-β₁, suggesting that arsenic preparation may exert positive effect on healing chronic skin ulcer through regulating collagen metabolism.     

Kinetics of pathologic changes in bleomycin-induced murine pulmonary fibrosis model

AIM: To Investigate the kinetics of pathologic changes in bleomycin-induced pulmonary fibrosis in rats. METHODS: Sixty male SD rats were randomized as a negative control group and pulmonary fibrosis model groups (B3, B7, B14, B28, B56 sub-groups). Except for control group, rats in the other groups were intratracheally administered with bleomycin. Animals in pulmonary fibrosis model groups were sacrificed on day 3, 7, 14, 28 and 56. The sections of the right lung were stained by HE, Masson and sirius red. The left lung was weighed and its hydroxyproline content was assayed. The mRNAs of TGF-β1, MMP-9 and TIMP-1 in the lung homogenate were measured by semi-quantitative RT-PCR. The expressions of TGF-β1, MMP-9 and TIMP-1 in lungs were observed by immunohistochemistry. RESULTS: (1) The content of lung hydroxyproline in pulmonary fibrosis model groups was significantly increased than that in control group (P<0.05). The pulmonary inflammation in pulmonary fibrosis model groups was significantly serious than that in control group, pulmonary fibrosis in B14, B28 and B56 groups was also significantly serious than that in control group. (2) A small quantity of TGF-β1, MMP-9 and TIMP-1mRNA were measured in normal lung, and the expression increased significantly after administration of bleomycin. Different expressions of TGF-β1, MMP-9 and TIMP-1 in different days after bleomycin administration were observed. CONCLUSION: The pathological changes in different days after bleomycin administration are different. TGF-β1, MMP-9 and TIMP-1 may play important roles in the pathogenesis of pulmonary fibrotic process.     

Effects of hydrogen sulfide on wound healing of skin ulcer in diabetic rats

AIM: To study the effect of hydrogen sulfide on wound healing of skin ulcer in diabetic rats.METHODS: Male SD rats were randomly divided into 3 groups, including non-diabetic control(NDC) group, untreated diabetic control(UDC) group, and treated diabetic administration(TDA) group. Diabetic rats were induced by intraperitoneal injection of streptozotocin(STZ). After 1 week, wound healing model was prepared by making a round incision(2.0 cm in diameter) on the dorsal skin in full thickness. The rats from TDA group received 2% sodium bisulfide ointment on the skin ulcer wound, and the animals from UDC and NDC groups received control cream. After 21 d of treatment with sodium bisulfide, blood samples were collected for biochemical analysis, including prothrombin time(PT), thrombin time(TT), and fibrinogen(FIB) in plasma, as well as the activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in the serum. White blood cells(WBC) and lymphocytes were also counted. Granulation tissues from the wound were processed for histological examination and Western blot analysis was used to detect heme oxygenase-1(HO-1) and tumor necrosis factor α(TNF-α) expression.RESULTS: Compared with UDC group, sodium bisulfide treatment accelerated wound healing of skin ulcer(P<0.01), and increased the activity of SOD in serum(P<0.01) in the diabetic rats. The declined number of WBC and lymphocytes, prolonged PT and TT, and decreased FIB levels in rats treated with sodium bisulfied were also confirmed. Pathological section showed that there were inflammatory cell infiltration, and irregular and loose fibril alignment in the granulation tissue of rats from the UDC group, but there were regular fibril alignment and increased angiogenesis in the granulation tissue of rats from the TDA group(P<0.05). Furthermore, sodium bisulfide treatment raised HO-1 protein expression, and decreased TNF-α protein expression in the diabetic rats.CONCLUSION: Hydrogen sulfide accelerates the wound healing of skin ulcer in the rats with diabetes. The beneficial effect of H₂S may be associated with formation of granulation, anti-inflammation, and antioxidation.     

Altered activity and expression of MMPs/TIMPs are associated with functional and structural left ventricular remodeling in hypertensive rats

AIM: To investigate the relationship between matrix metalloproteinases and tissue inhibitors of matrix metalloproteases imbalance with functional and structural left ventricular (LV) remodeling in the hypertensive rats.METHODS: 6-week-old male stroke-prone spontaneously hypertensive rats (SHR-SPs,n=40) served as the hypertensive heart disease model,and age-matched male Wistar-Kyoto (WKY) rats (n=10) were used as control.After 6 months,the rats in two groups were anesthetized for invasive hemodynamic measurement by Millar pressure-volume (P-V) conductance catheter.Then the rats were sacrificed and hearts were dissected for morphological analysis,gelatin-zymography and Western blotting analysis.RESULTS: Left ventricular (LV) hemodynamic parameters showed the systolic and diastolic dysfunction in SHR-SPs compared with that in control group (P<0.05).Collagen volume fraction,ratio of perivascular collagen area to luminal area,myocardial cross-sectional area and the medial area to luminal area ratio of the SHR-SPs were all increased remarkably (P<0.05).LV matrix metalloproteinase-2 (MMP-2) activities,MMP-2 and tissue inhibitors of matrix metalloprotease-1 (TIMP-1) protein level in SHR-SP were notably higher than those in control group (P<0.05).CONCLUSION: Chronic pressure-overload is capable of inducing imbalances of cardiac ECM and MMPs/TIMPs system,both imbalances induce LV dilation,cardiac systolic and diastolic dysfunction.     

Expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in lung tissue of hypercapnia rat model

AIM: To study the expression of matrix metalloproteinase-9(MMP-9), matrix metalloproteinase-2(MMP-2) and the tissue inhibitor of metalloproteinase(TIMP-1) in the lung tissue of the hypercapnia rat.METHODS: Forty Wistar rats were randomly divided into a control group (group A, n=20) and hypercapnia group (group B, n=20). Group B received mix gas exposure (6% CO2, 21% O2, 72% N2) 7 h daily for 4 weeks. The parameters we would examine were as follow: arterial blood gas; the mean pulmonary artery pressure;MMP-2,MMP-9, TIMP-1, and NE activity in lung tissue. Masson pigmentation of elasticity fibre was analyzed by computer image analyzer. Histopathological changes of lung tissue were observed under light microscope. The protein expression of MMP (MMP-2, MMP-9) and TIMP (TIMP-1) in lung tissue were determined by immunocytochemistry.RESULTS: Decompensate respiratory acidosis (pH=7.20±0.04, PaCO2=7.84±0.15) developed in group B. The mean pulmonary artery pressure were similar between groups B and A (P>0.05). Tissue edema in the lung, endothelial cell damage of the small blood vessels, pulmonary micro thrombus formations and increased pulmonary capillary permeability were observed in group B. NE activity increased significantly (P<0.01). However, no significant change of MMP-2, MMP-9, TIMP-1 activity was found in group B and group A (P>0.05). There was significant decrease in the relative content of elasticity fibre in lung tissue in group B compared to group A (P<0.01). The expression of MMP-2 protein in the lung tissue of group B was lower than that in group A (P<0.01), but the expression of both MMP-9 and TIMP-1 proteins in the lung tissue in group B were higher than those in group A (P<0.01).CONCLUSION: Hypercapnia rat model is successfully reproduced by exposure of animals to the mix gas exposure (6% CO2, 21% O2, and 72% N2). The pulmonary artery pressure is not affected by hypercapnia. High concentration of CO2 causes increase of NE activity and decrease in the relative content of elasticity fibre. High concentration of CO2 causes the increase of MMP-2 protein expression and decrease in the MMP-9 and TIMP-1 protein expression.     

Regulation by reactive oxygen species of matrix metalloproteinase-1, 3 and tissue inhibitor of matrix metalloproteinase-1 in smooth muscle cells

AIM: To understand whether reactive oxygen species promote the rupture of atherosclerotic plaques by regulating the balance of matrix metalloproteinase-1, 3 (MMP-1, 3) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in smooth muscle cells. METHODS: Aortic smooth muscle cells from 4-6months-healthy abortive fetuses were incubated for 24 hours with xanthine (100 μmol/L) and xanthine oxidase (5 U/L) in vitro . MMP-1, 3 and TIMP-1 in the concentrated culture media were measured by Western blotting ( n =3 independent experiments). RESULTS: Incubation with xanthine/xanthine oxdiase decreased the amount of MMP-1 in the aortic smooth muscle cells (21.2%±5.5% of the control group), and pro-MMP-1 was activated completely. Reactive oxygen species (ROS) also activated pro-MMP-3, and increased the production of MMP-3 in the aortic smooth muscle cells. On the other hand, ROS inhibited the production of TIMP-1 in the aortic smooth muscle cells. CONCLUSION: It is complicated that ROS regulates the balance of MMPs and TIMPs. ROS may contribute to matrix degradation and the rupture in the atherosclerotic plaques.     

Activation of α7nAChR promotes wound healing in diabetic mice by suppressing TNF-α expression

AIM: To explore the role of α7 nicotinic acetylcholine receptor (α7nAChR)-specific agonist PNU-282987 in promoting wound healing in diabetic mice by suppressing the expression of tumor necrosis factor α （TNF-α）.METHODS: A model of incised wound was established in diabetic mice or normoglycaemic mice (control). Skin samples were taken on 1 d, 3 d, 5 d, 10 d, 14 d and 21 d post-injury (5 mice in each posttraumatic interval). The numbers of macrophages and fibroblasts, the expression of TNF-α and the deposition of collagen were detected by the methods of immunohistochemistry, Western blotting and Masson staining, respectively. After incised wound was performed in the diabetic mice, PNU-282987 was applied by intraperitoneal injection at suitable posttraumatic interval. The above indexes were investigated again.RESULTS: Compared with control group, the diabetic mice presented delayed wound healing. In diabe-tic mice, the infiltration of macrophages and the expression of TNF-α were significantly reduced in the early phase during wound healing, while they were significantly increased from 5 d post-injury. Besides, from 5 d to 21 d post-injury, the wounds in diabetic mice showed decreased number of fibroblasts and deposition of collagen. From 5 d post-injury, PNU-282987 was applied to diabetic mice, which significantly down-regulated the expression of TNF-α, and increased the number of fibroblasts and the content of collagen in the wounds, eventually promoted wound healing.CONCLUSION: Inflammatory reactions delay wound healing in diabetic mice. Activation of α7nAChR promotes wound healing in diabetic mice by suppressing the expression of TNF-α.     

Relationship between matrix metalloproteinase-9 and tissue metalloproteinase inhibitor-1 and carotid atheromatous plaque stability

AIM: To investigate the correlation between matrix metalloproteinase-9 (MMP-9),tissue metalloproteinase inhibitor-1 (TIMP-1),MMP-9/TIMP-1 and carotid atheromatous plaque stability in cerebral infarction patients.METHODS: 80 patients with cerebral infarction were categorized as microemboli-negative group (n=70) and microemboli-positive group (n=10),20 normal human were served as control group.The MMP-9 and TIMP-1 levels in plasma were determined by mean of ELISA in 3 groups.RESULTS: The levels of MMP-9 and TIMP-1 in plasma were significantly higher in cerebral infarction patients than those in control group (P<0.01).The plasma MMP-9 content was positively correlated with TIMP-1 content (r=0.76，P<0.01).The ratio of MMP-9/TIMP-1 increased only in microemboli-positive patients (P<0.01).CONCLUSION: The results indicate that the plasma MMP-9 participates in pathophysiological process of cerebral infarction.The ratio of MMP-9/TIMP-1 shows a close relationship with carotid atheromatous plaque instability.     

Decreased fibroblast proliferation and collagen content in the wound of diabetic rats caused by streptozotocin

AIM: To study fibroblast proliferation and collagen synthesis during wound healing in diabetic rats induced by streptozotocin. METHODS: 30 Wistar male rats were randomly divided into control group and model group. 55 mg/kg STZ were given intraperitoneally to model rats. After 3 weeks, a round skin of 2.04 cm2 was excised on all dorsal back of rats. The healing time and healing rate were observed according to re-epithelization. The numbers of fibroblasts and the expression of proliferating cell nuclear antigen (PCNA) were observed by Hematoxylin-Eosin (HE) staining and immuno-histochemistry assay. Collagen Ⅰ and Ⅲ stained by Picric acid-Sirius red were calculated by image analysis. RESULTS: The healing time in model group was (27.13±1.81) days，significantly longer than that in control group ［(15.25±1.67） days， P<0.01］. The healing rates in model group were significantly less than that in control group at day 3, day 7 and day 15 (P<0.01). The amount of fibroblasts and the expression of PCNA in model group were significantly less than those in control group on day 3, day 5, day 7 and day 9, respectively (P<0.05, P<0.01). Even the content of collagen I in the wound of both groups increased with time, the values were much higher than that in model group at different times (P<0.05), respectively. For model group, the ratio of collagen Ⅰ/Ⅲ was less than that in control group 3, 7 and 11 days after wound (P<0.01). CONCLUSION: STZ impaires wound healing in rats, which is possible caused by the disturbance of fibroblast proliferation and collagen synthesis in the wound.     

Effect of JNK/MCP-1 signaling pathway on anti-diabetic neuropathic pain by curcumin in type 2 diabetic rats

AIM:To investigate the effect of JNK/MCP-1 signaling pathway on anti-diabetic neuropathic pain by curcumin in type 2 diabetic rats. METHODS:The male Sprague-Dawley rats were induced as the model of the type 2 diabetic neuropathic pain rats, they were randomly divided into 6 groups (n=27): type 2 diabetic neuropathic pain (DNP) group, type 2 diabetic neuropathic pain and intraperitoneal injection of curcumin (Cur) group, type 2 diabetic neuropathic pain and solvent control (DSC) group, type 2 diabetic neuropathic pain and JNK inhibitor (DJ) group, type 2 diabetic neuropathic pain and JNK inhibitor solvent control (DJS) group, type 2 diabetic neuropathic pain and monocyte chemoattractant protein 1 (MCP-1) agonist (DM) group. Another 27 normal SD rats were selected as control group. Mechanical withdrawal threshod and thermal withdrawal latency were measured at 3rd d, 7th d and 14th d after dosing, then the lumbar segment 4~6 of the spinal cord and L4~6 DRG were removed at the same time. ELISA was used to measure MCP-1 level. The expression of p-JNK was determined by Western blotting. RESULTS:Compared with DNP group, p-JNK was significantly decreased at 7th d and 14th d in Cur group, DJ group and DM group after treatment (P<0.05). Compared with C group, the MCP-1 was significantly declined in other 6 group after streptozotocin injection (P<0.05). Compared with DNP group, MCP-1 were significantly increased at 7th d and 14th d in Cur group and DJ group after treatment (P<0.05), and that in DM group was greatly decreased (P<0.05). CONCLUSION: The expression of p-JNK and MCP-1 was increased in DNP rats with spinal cord and dorsal root ganglion. The mechanism of curcumin reducing the neuropathic pain in type 2 diabetic rats might be through regulating the JNK/MCP-1 pathway.     

Ulinastatin protects rat pulmonary tissues from paraquat-induced acute injury

AIM: To investigate the protective effects of ulinastatin on the rats with paraquat-induced acute lung injury and its mechanisms. METHODS: The Wistar rats (n=108) were randomly divided into control group, paraquat group and ulinastatin group. The rats in paraquat group and ulinastatin group were given paraquat by gavage, while the rats in control group were given sterile saline by gavage. The rats in ulinastatin group were also given ulinastatin treatment. The serum levels of MDA, SOD, IL-6, IL-10 and TNF-α were measured after 1 d, 3 d, 7 d, 14 d, 21 d and 28 d. The expression levels of p38 MAPK, MMP-2 and TIMP-1 in the lung were also measured. RESULTS: The levels of SOD in 1 d, 3 d and 7 d in paraquat group and ulinastatin group were significantly lower than those in control group (P<0.01). The level of SOD in ulinastatin group was significantly higher than that in paraquat group (P<0.05). The levels of MDA, IL-6, IL-10 and TNF-α in 1 d, 3 d and 7 d in paraquat group and ulinastatin group increased compared with control group (P<0.01), and those in ulinastatin group were significantly lower than those in paraquat group (P<0.05). The levels of p38 MAPK and TIMP-1 in 1 d, 3 d, 7 d, 14 d, 21 d and 28 d in paraquat group and ulinastatin group were higher than those in control group (P<0.01), and those in ulinastatin group was significantly lower than those in paraquat group (P<0.05). The level of MMP-2 in 1 d, 3 d, 7 d, 14 d and 21 d in paraquat group and ulinastatin group increased compared with control group (P<0.01), and that in ulinastatin group was significantly lower than that in paraquat group (P<0.05).CONCLUSION: Ulinastatin protects the lung tissues of rats from paraquat-induced acute lung injury by inhibiting p38 MAPK signaling pathway and ameliorating inflammatory and oxidative responses.     

Coriaria sinica Maxim extract promotes burn wound healing in rats

AIM：To investigate the effects of Coriaria sinica Maxim extract (CSME) on burn wound healing in rats. METHODS：Forty male SD rats were randomly divided into normal saline (NS) group, white petrolatum jelly (WPJ) group, silver sulfadiazine (SSD) group and CSME group. After the animals were anesthetized, the skin of their backs was burnt to induce deep Ⅱ degree burn wounds. These wounds were treated respectively for 21 d by covering dressings with NS, WPJ, SSD and CSME, respectively. On the 1st, 3rd, 7th, 14th and 21st days, after the clinical symptoms of the animals and conditions of the wounds such as the epithelization rate, crusting and hair growth were observed, the wound tissues were also taken for histological examination. The content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the expression of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and collagen were detected. RESULTS：On the 21st day after burn, the new epithelial tissues in CSME group extraordinarily　developed and a great deal of hair also grew along the margin of the wounds. The epithelization rate of the wound tissues in CSME group was higher than that in other groups. There was rare new hair in the center of the wound area in SSD group, but intensive new hair was observed in CSME group. On the 14th day and 21st day after burn, multilayer of epithelial cells was entirely covered with the wound area in CSME group. Some of the healing signs, such as sufficient differentiation and a line up in order of collagen fibers, clear tissue structure, exceedingly active hyperplasia of sebaceous glands and hair follicles, and so on, were also observed in the wound area in CSME group. From the 1st day to 21st day after burn, the increase in protein expression of EGF and bFGF in the wound tissues was significantly higher than that in other groups in the early stage, which was quickly decreased and was obviously lower than other groups in the latter stage. The mRNA expression ratio of type I and III collagens in SSD group was significantly higher than that in other groups, while that in CSME group was significantly lower than that in other groups. CONCLUSION：CSME promotes burn wound healing without scarring. The effects of CSME are likely to associate with the expression reinforcement of EGF and bFGF at mRNA and protein levels in the early stage, and associate with the expression inhibition of them later. Moreover, CSME may also inhibit the mRNA expression of type I collagen and promote the synthesis of type III collagen in the wound tissues of burn.