Endothelial progenitor cell-conditioned medium improves lung structure in neonatal rats exposed to hyperoxia

AIM: To investigate the therapeutic effect of endothelial progenitor cell-conditioned medium (EPC-CM) on the lung structure of neonatal rat exposed to hyperoxia, and to explore the mechanisms.METHODS: Bone marrow-derived endothelial progenitor cells (EPCs) were collected from new born Sprague-Dawley (SD) rats and the EPCs were identified. The conditioned medium from the passage 3 EPCs was collected. Newborn SD rats (n=40) were randomly divided into 4 groups. The rats in room air group were exposed to the room air (21% O₂) for 21 d. The rats in hyperoxia group were exposed to hyperoxia (85% O₂) for 21 d. The rats in endothelial cell basal medium (EBM) group were exposed to hyperoxia for 21 d, and received 100 μL EBM on postnatal day 14 (P14) in a single intratracheal (IT) injection. The rats in EPC-CM group were exposed to hyperoxia for 21 d, and received 100 μL EPC-CM on P14 in a singlie IT injection. The rats were sacrified on the 21st day. The left lungs were excised, placed in 4% paraformaldehyde, serially dehydrated in ethanol and embedded by paraffin. Serial sectioning of the paraffin-embedded left lung tissues was prepared for 5 μm thickness, and stained with hematoxylin and eosin. The pulmonary radical alveolar count (RAC) and alveolar mean linear intercept (MLI) were then calculated. The microvascular density was determined by FVⅢ immunostaining. The mRNA expression of KGF, VEGF, SP-A and SP-C in the right lung tissues was detected by real-time fluorescence quantitative PCR. RESULTS: The cultured cells had typical EPC morphological characteristics, and had the abilities to bind to FITC-UEA-1 and uptake DiI-ac-LDL. The body weight of the rats on day 21, RAC, MLI and microvascular density were significantly lower in hyperoxia group and EBM group than those in room air group (P<0.05). The EPC-CM group had significantly higher RAC and microvascular density than those in hyperoxia group and EBM group (P<0.05), but the body weight and MLI had no significant difference. The mRNA expression levels of KGF, VEGF, SP-A and SP-C in hyperoxia group and EBM group were significantly lower than those in room air group (P<0.05). The mRNA expression levels of KGF, VEGF, SP-A and SP-C in EPC-CM group were significantly higher than those in hyperoxia group and EBM group (P<0.05). CONCLUSION: EPC-CM promotes the lung alveolarization and microvascular formation in neonatal rats exposed to hyperoxia. These benefits may be correlated with the increased KGF and VEGF mRNA expression.     

Effect of acupuncture on expression of EGF and bFGF in brain tissues of rats with traumatic brain injury

AIM: To observe the effect of acupuncture on the expression of epidermal growth factor (EGF) and basic fibrolblast growth factor (bFGF) in the brain tissues of rats with traumatic brain injury. METHODS: Thirty SD rats were randomized into sham-operated group, model group and acupuncture group. The model of traumatic brain injury was established by free drop impact. Acupuncture was performed to the rats in acupuncture group once every day and 7 days altogether. Brain histotomy was conducted after the treatment. Immunohistochemical method was adopted to test the protein expression of EGF and bFGF. RESULTS: Compared to sham-operated group, the expression of EGF in the brain tissues of model group decreased (P<0.01), and the expression of bFGF increased (P<0.01). Compared to model group, the expression of EGF and bFGF in acupuncture group increased obviously (P<0.01). CONCLUSION: Acupuncture significantly increases the expression of EGF and bFGF, and improves the repair of injured brain tissues. This might be one of the mechanisms by which acupuncture can treat traumatic brain injury and improve the nervous function.     

Effect of ischemic post-conditioning on Egr-1 and IL-1β expression in ischemia-reperfusion injured lung in rats

AIM: To investigate the protective effects of ischemic post-conditioning on the expression of early growth response factor 1 (Egr-1) and interleukin-1β(IL-1β) in ischemia-reperfusion injured lung in rats. METHODS: The model of lung ischemia-reperfusion injury was established in 24 rats and the rats were randomly allocated to 3 different groups (n=8 in each group): (1) sham group: only sham operation (thoracotomy) and no ischemia for 3 h; (2)ischemia-reperfusion group (I/R group): interruption of pulmonary perfusion and ventilation for 1 h followed by reperfusion for 2 h; (3) ischemic post-conditioning group (IPostC group): ischemic post-conditioning (5 min of reperfusion and 5 min of ischemia for 3 times) between the end of ischemia and the beginning of the reperfusion followed by reperfusion for 1.5 h. The lung tissues (prepared to small pieces of about 20 mg) were collected and homogenized at the end of the experiment. The concentration of myeloperoxidase (MPO) in the homogenate was determined. The wet to dry weight ratio (W/D) of the lung tissues was also measured at the end of reperfusion. The pathological changes of the lung tissues were observed under light microscope after reperfusion. The mRNA expression of Egr-1 and IL-1β in the lung tissues was detected by RT-PCR. RESULTS: Compared with sham group, the mRNA expression of Egr-1 and IL-1β, the levels of MPO and W/D were significantly increased in I/R group (P<0.05). The inflammatory responses of the lungs in I/R group were significantly severer than those in sham group. Compared with I/R group, the mRNA expression of Egr-1 and IL-1β, the levels of MPO and W/D in IPostC group were significantly decreased (P<0.05). The inflammatory responses of the lungs in IPostC group were also significantly attenuated. CONCLUSION: Ischemic post-conditioning significantly reduces ischemic reperfusion injury of the lung by inhibiting the expression of Egr-1 and IL-1β.     

Effect of ghrelin on iNOS expression in alveolar macrophages and lung tissues in rats with sepsis-associated lung injury

AIM: To investigate the effect of ghrelin on inducible nitric oxide synthase (iNOS) expression in alveolar macrophages and lung tissues in sepsis-induced acute lung injury (ALI) rats. METHODS: The septic rat model was established by cecal ligation and puncture (CLP). Male SD rats were divided into sham group, CLP group and CLP+ghrelin group. The rats in the former 2 groups were further divided into 3 subgroups, which were 6 h, 12 h and 20 h post-operation groups. Ghrelin was administered by intraperitoneal injection at 3 h and 15 h after operation in ghrelin group. The samples were harvested 20 h after operation. The mRNA expression of iNOS in alveolar macrophages collected from bronchoalveolar lavage was detected by RT-PCR. The protein levels of lung iNOS were measured by Western blotting. The lung pathological examination was performed 20 h after operation. RESULTS: In CLP group, the mRNA expression levels of iNOS in the alveolar macrophages were 1.33±0.05, 1.44±0.08, 1.57±0.11 at 6 h, 12 h and 20 h after CLP, respectively, which were higher than that in sham group, but did not show time correlation. However, it was lower in CLP group than that in CLP+ghrelin group at 20 h after CLP (2.27±0.37, P<0.05). At 20 h after CLP, the protein level of lung iNOS was decreased in CLP+ghrelin group (0.87± 0.03) as compared with CLP group (1.08±0.05). Compared with sham group, the histopathological score was increased in both CLP group and CLP+ghrelin group, but it was lower in CLP+ghrelin group (5.83±0.477) than that in CLP group (7.83±0.75). CONCLUSION: Ghrelin treatment improves the degree of ALI. During 6 h to 20 h after CLP, the mRNA expression of iNOS in alveolar macrophages was elevated, but the difference was not seen as the time went on. Ghrelin up-regulates the mRNA expression of iNOS in alveolar macrophages and inhibits iNOS expression in lungs of septic rats.     

会讯

AIM:To investigate the pulmonary expresson of macrophage migration inhibitory factor(MIF) in acute lung injury (ALI) rats induced by intravenous injection of oleic acid and its correlation with blood gas change, pulmonary weight index (PWI) and pulmonary pathological injuries.METHODS: ALI rats model were made by injecting oleic acid as the oleic acid group while rats injection with saline solution as control. After injecting oleic acid or saline for six hours, the PaO₂ and PaCO₂ of the left heart and pulmonary weight index were measured. At the same time, by using a microwave-base double immunohistochemistry labeling, the number of MIF^＋, ED₁⁺ (anti-CD68 antibody), ED₁⁺/MIF^＋cell in pulmonary tissue of different groups and their correlation with blood gas and pulmonary weight index were examined. RESULTS: The blood gas parameters of the oleic acid group were far worse than that of the control group (P＜0.01). The PWI of the oleic acid group was significantly higher than that of the control group (P＜0.01). There was marked upregulation of MIF expression on injured lung tissue. The number of cell expressed MIF^＋ , ED₁⁺ and MIF with ED₁ showed a strong positive correlation with PaO₂, PWI and histological changes. CONCLUSION: MIF may play a pivotal role in mediation of progressive lung injuries induced by intravenous oleic acid injection. In addition, the number of cells expressed MIF, especially macrophage, may reflect the severity of lung injury.     

Effect of Ginkgo biloba extract on the expression of connective tissue growth factor in the initiating stage of fibrosis in lungs of rats

AIM: To study the effect of Ginkgo biloba extract (GbE) on the expression of connective tissue growth factor (CTGF) in the initiating stage of pulmonary fibrosis of rats after administration of bleomycin (BLM).METHODS: The expression of CTGF in lungs was detected by Western blotting. The content of hydroxyproline was assayed by the method of chloramines T. The content of malondialdehyde (MDA) in plasma was investigated by colorimetry.RESULTS: On day 14 after administration of BLM, the contents of CTGF in lungs and MDA in plasma in BLM+NS group were higher than those in NS group, respectively (P<0.05; P<0.01). On day 30 after BLM, the contents of hydroxyproline in lungs and MDA in plasma in BLM+NS group were higher than those in NS group, respectively (both P<0.01). Treatment with GbE ameliorated the above changes induced by BLM. CONCLUSION: GbE ameliorates the up-regulation of CTGF in the initial stage of fibrosis in lungs of rats after administration of BLM. GbE prevents the hyperoxidative injury in lungs of rats after BLM, which might be one of mechanisms underling the effect of GbE on CTGF.     

Effect of microcapsulated catechin on expression of vascular endothelial growth factor in rats with adriamycin induced-nephrotic syndrome

AIM: To study the effect of microcapsulated catechin on vascular endothelial grower factor (VEGF) expression in rats with adriamycin induced-nephrotic syndrome.METHODS: 120 female SD rats were randomly distributed in control group,nephrotic group,dexamethason group,vitamin E group,catechin group and microcapsule group.Rat with nephrotic syndrome were induced by injection of adriblastine (5 mg/kg BW).VEGF concentrations in serum and urine were detected by ELISA assay.VEGF expression in kidney was measured by immunohistochemistry assay.RESULTS: At the end of 4th week and 6th week,VEGF concentration in other groups in kidney,serum and urine were higher than that in control (all P<0.01),and were lower than that in nephritic group (exclude Vit E group,all P<0.01).Serum and urine VEGF concentrations in microcapsule group were lower than those in catechin group (P<0.01,P<0.05,respectively).VEGF expression in microcapsule group in kidney was lower than that in catechin group,but it was not significant different.Urinary protein excretion at 24 h in microcapsule group was lower than that in catechin group (P<0.05),there was positive correlation among urine protein,serum VEGF level,urine VEGF concentration and renal VEGF expression at 24 h (all P<0.01).CONCLUSION: Catechin decreases urinary protein excretion in the rats with nephrotic syndrome through reducing the expression and secretion of VEGF.Microcapusulated catechin is benefit in decreasing the expression and secretion of VEGF.     

Endogenous basic fibroblst growth factor is a protective factor against myocardial ischemia/reperfusion injury of rats

AIM: To observe the role of exogenous and endogenous basic fibroblst growth factor (bFGF) on myocardial ischemia/reperfusion(I/R) injury of rats.METHODS:bFGF and bFGF antiserum were applied to rat isolated I/R heart. Myocardial function, coronary effluent volume,protein and myoglobin content as well as LDH activity in coronary effluent fluid, myocardial calcium, MDA and ATP concentration as well as PKC, MAPK activity were measured. RESULTS:Compared with control, myocardial function in I/R group significantly decreased. Protein, myoglobin content and LDH activity in coronary effluent liquid as well as myocardial MDA and calcium content increased, while myocardial ATP concentration decreased(all P＜0.01). Compared with I/R group, ±LV dp/dt_max in bFGF group increased by 43% and 26%, respectively. LVEDP decreased by 40%. HRr/HRi and B/A augmented by 42% and 20%, respectively. Protein and myoglobin content as well as LDH activity lowered by 29%,30％ (all P＜0.01) and 33％ (P＜0.05) respectively. Myocardial MDA and calcium content decreased by 44% and 35%, respectively, while myocardial ATP level as well as PKC and MAPK activity increased by 34%,41％ and 10% (all P＜0.01), respectively. In bFGF antiserum group, ±LV dp/dt_max were 35% and 38% lower than those in I/R group. LVEDP increased by 93%. HRr/HRi and B/A decreased by 36% and 45%, respectively. Protein and myoglobin content as well as LDH activity augmented by 54%,96％ (all P＜0.01) and 34％ (P＜0.05) respectively. Myocardial MDA and calcium content increased by 24% and 50%, respectively, while myocardial ATP level as well as PKC and MAPK activity lowered by 28%,21％ and 8% (all P＜0.01), respectively. CONCLUSION:Endogenous bFGF is a protective factor against myocardial ischemia/reperfusion injury of rats.     

Nerve growth factor attenuates cochlear injury induced by brain ischemia and reperfusion in rats

AIM: To investigate the effect of nerve growth factor (NGF) on auditory and cochlear damage induced by brain ischemia and reperfusion. METHODS: The rats with brain ischemia and reperfusion were divided into two groups at random. In the experimental group, the rats were injected intramuscularly with NGF . In control group, the animals were injected with normal saline instead of NGF. Then the hearing loss and cochlear structural changes of rats in both groups were compared. RESULTS: It was found that the hearing loss of rats in NGF group were less significantly than that of control group ( P< 0.01) after 60 min and 24 h reperfusion following 30 min ischemia. Scanning and transmission microscopy showed that the damage of the outer hair cells and the spiral neurons of rats in NGF group was much slighter than that of control group. CONCLUSION: NGF prevents auditory and cochlear injury induced by brain ischemia and reperfusion.     

Effect of inhibiting mTOR signaling pathway on p-AKT1 molecule in lung of juvenile SD rats and its significance

AIM:To investigate the effect of inhibiting mammalian target of rapamycin (mTOR) signaling pathway on phosphorylated AKT1 (p-AKT1) during lung injury induced by hyperoxygen in juvenile SD rats and its significance. METHODS:The SD rats (3 weeks old, n=72) were randomly divided into air + saline group, hyperoxia + saline group, hyperoxia + OSI-027 group, and hyperoxia + rapamycin group (n=18 in each group). The animal model was constructed by continuous intervention with a 90% volume fraction of oxygen, and normal saline, OSI-027 and rapamycin were administered by intraperitoneal injection at 1, 3, 6, 8, 10 and 13 d of the observation period. At 3, 7 and 14 d, the changes of the body weight, wet/drg weight ratio (W/D), lung histopathology, alveolar septal width and lung injury score were measured, and immunohistochemistry and Western blot were used to detect the distribution and protein levels of phosphorylated S6K1 (p-S6K1) and p-AKT1 in the lung tissues. RESULTS:Compared with air group, the body weight of the rats in hyperoxia group was significantly decreased (P<0.05), the lung W/D was increased in the acute phase of lung injury (P<0.05), and the alveolar septal width and lung injury scores were significantly increased (P<0.05). The p-S6K1 positive cells in the lung tissues were increased (P<0.05), p-AKT1 positive cells were decreased (P<0.05), p-S6K1 protein was increased significantly (P<0.01), and p-AKT1 protein was decreased significantly (P<0.01). Compared with hyperoxia group, the lung tissue injury in hyperoxia + OSI-027 group was alleviated (P<0.05), p-S6K1 positive cells in the lung tissues was decreased (P<0.05), p-AKT1 positive cells was increased (P<0.05), p-S6K1 protein level was significantly decreased (P<0.05), and p-AKT1 protein level was increased (P<0.05). Hyperoxia+rapamycin further aggravated lung injury (P<0.05), p-S6K1 positive cells decreased (P<0.05), p-AKT1 positive cells increased (P<0.05), p-S6K1 protein levels decreased significantly (P<0.05), and p-AKT1 protein levels increased significantly (P<0.05). Compared with hyperoxia + rapamycin group, the lung tissue damage was alleviated in hyperoxia + OSI-027 group (P<0.05), p-AKT1 positive cells in the lung tissues were decreased (P<0.05), and p-AKT1 protein level was decreased (P<0.05). CONCLUSION:p-AKT1 may be involved in the development of hyperoxia-induced lung injury, and its regulation mechanism may be related to the mTOR signaling pathway. In hyperoxia-induced lung injury, the protein level of p-AKT1 is decreased, and mTOR inhibitors increase the p-AKT1 protein. However, only the mTORC1/2 dual inhibitor OSI-027 alleviates the hyperoxia-induced fibrosis in juvenile SD rats.     

Effect of hyperlipidemia on nitric oxide levels of blood and myocardial tissues in rats

AIM: To study the impact of hyperlipidemia on vasoactive substances and the mechanism of gemfibrozil in regulating the endothelial function. METHODS: The hyperlipidemic model was established with rats. The serum levels of lipid, NO, angiotensin Ⅱ (Ang Ⅱ), vascular endothelial growth factor(VEGF) and levels of NO, AngⅡ in myocardial tissues were measured. RESULTS: Hyperlipidemic rats had lower level of NO and higher level of VEGF than control subjects. Significant correlation had been shown between serum levels of lipid and NO. Administration of gemfibrozil significantly elevated serum VEGF, NO and myocardial tissue NO levels. CONCLUSIONS: Hyperlipidemia not only reduced serum NO level but also reduced myocardial NO content, which could cause endothelial dysfunction. Gemfibrozil reversed the above changes induced by hyperlipidemia, which might have relevance to VEGF.     

Effects of NG-nitro-L-arginine on LPS-induced lung injury in rats

AIM: To investigate the effects of nitric oxide (NO) and NO synthase (NOS) inhibitor N^G-nitro-L arginine (L-NA) on LPS induced-lung injury in rats. METHODS: Forty healthy male SD rats, weighing 300±20 g, were used. The animals were anesthetized with 20% urethane 1 g·kg^-1. Common carotid artery (CAA) and jugular vein were exposed through a median incision in the neck. Mean arterial pressure (MAP) was measured through a pressure transducer connected with intubation of CAA. The animals were randomly divided into five groups: group 1: control; group 2: LPS (5 mg·kg^-1, iv); group 3: high dose L-NA (20 mg·kg^-1 intraperitoneal injection, ip); gropu 4: middle dose L-NA (10 mg·kg^-1, ip); group 5: low dose L-NA (5 mg·kg^-1, ip). Group1 : 0.9% saline solution was given and the animals were killed 6 h after the saline solution. Gruop 2: saline solution was given 3 h after LPS and the animals were killed 3 h after administration. Group 3, 4 and 5: L-NA was given 3 h after LPS iv and the animals were killed 3 h after administration, respectively. The pulmonary was removed immediately. The pulmonary coefficient and water content in pulmonary tissue were calculated (%). The NO₂^-/NO₃^- content in plasma, MDA content and NOS, SOD activity in the pulmonary tissue were measured. RESULTS: L-NA significantly decreased pulmonary coefficient and water content in pulmonary tissue and ameliorated LPS induced lung injury. The effect in high dose group was better than that in low dose group. L-NA significantly decreased NO₂^-/NO₃^- content in plasm, decreased MDA content and inhibited NOS activity and enhanced SOD activity in the pulmonary tissue. CONCLUSION: It may be concluded that L-NA has a beneficial effect on lung injury induced by LPS.     

Effect of all-trans-retinoic acid on the proliferation and expression of α-SMA in human embryonic lung fibroblasts

AIM: To investigate the effects of all-trans-retinoic acid (ATRA) on the proliferation and differentiation of transforming growth factor β₁(TGF-β₁)-stimulated human embryonic lung fibroblasts (HFL-I).METHODS: The HFL-I cells were cultured in vitro and were pretreated with ATRA for 3 days at the concentrations of 0.1 μmol/L, 1 μmol/L and 10 μmol/L. The proliferation of HFL-1 cells was detected by MTT method. The mRNA expression of α-smooth muscle actin(α-SMA) in HFL-I cells stimulated with TGF-β₁ for 0 h, 6 h, 12 h, 24 h, 48 h and 72 h was detected by RT-PCR and the protein expression of α-SMA at the time points of 1,3 and 5 days was detected by Western blotting. The mRNA expression of α-SMA in HFL-I cells pretreated with different concentrations of ATRA for 24 h was detected the by RT-PCR and the protein expression at time point of 3rd day was detected by Western blotting. RESULTS: Different concentration of ATRA inhibited the proliferation of HFL-I in a dose-dependent manner (P<0.05). Both mRNA and protein expression of α-SMA in HFL-I cells pretreated with TGF-β₁ was up-regulated (P<0.05). ATRA down-regulated the mRNA and protein expression of α-SMA induced by TGF-β₁ in a dose-dependent manner (P<0.05). CONCLUSION: ATRA inhibits the proliferation and TGF-β₁-stimulated differentiation in HFL-I cells by down-regulating the mRNA and protein expression of α-SMA.     

Relationship of expression of extracellular matrix metalloproteinase inducer and hepatocyte growth factor with lymphoid metastasis and prognosis in non-small-cell lung carcinoma

AIM: To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and hepatocyte growth factor (HGF) in non-small-cell lung carcinoma (NSCLC) and their relationship with lymphoid metastasis and prognosis.METHODS: Expression of EMMPRIN and HGF in 77 cases of patients with NSCLC was detected immunohistochemically.The relationship of expression of EMMPRIN and HGF with tumor size,smoking,histological type,differentiation,lymphoid metastasis,clinical stage,and prognosis was analyzed.RESULTS: The expressive rates of EMMPRIN and HGF were 68% and 44%,respectively.The expressions of EMMPRIN and HGF were associated positively with lymphoid metastasis (r=0.371 and 0.339，P＜0.01),and inversely with survival time (P＜0.01).No relationship was found between the expression of EMMPRIN,HGF and smoking,tumor size,histological type and differentiation (P＞0.05).The expression of EMMPRIN was associated with the expression of HGF in NSCLC.CONCLUSION: The expression of EMMPRIN and HGF is associated with lymphoid metastasis and prognosis in NSCLC.Overexpression of EMMPRIN and HGF implies infavourable prognosis in NSCLC.     

Impact of hydrogen sulfide donor on endothelin-1 and connective tissue growth factor expression in rats with pulmonary hypertension induced by high pulmonary blood flow

AIM: To explore the possible impact of hydrogen sulfide (H2S) donor-sodium hydrosulfide (NaHS) on endothelin-1 (ET-1) and connective tissue growth factor (CTGF) expressions in rats with pulmonary hypertension induced by high pulmonary blood flow. METHODS: Thirty-two male SD rats were randomly divided into 4 groups: shunt group, shunt+NaHS group, sham group and sham+NaHS group. Rats in shunt group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena cava shunt to create an animal model of high pulmonary flow. After 11 weeks of experiment, rat systolic pulmonary artery pressure (SPAP), lung tissue H2S, plasma ET-1 concentration and lung tissue ET-1mRNA expression, as well as pulmonary artery CTGF protein expression were detected.RESULTS: After 11 weeks of experiment, SPAP, lung tissue ET-1mRNA, plasma ET-1 as well as pulmonary artery CTGF expressions were increased markedly, respectively, whereas H2S in lung tissue decreased significantly in rats of shunt group as compared with that in sham group (all P<0.05). After administration of NaHS for 11 weeks, H2S in lung tissue increased significantly, whereas SPAP, plasma ET-1 and lung tissue ET-1 mRNA expression as well as pulmonary artery CTGF protein expression decreased significantly, respectively, in rats of shunt+NaHS group as compared with that in shunt group (all P<0.05).CONCLUSION: NaHS might be involved in the development of pulmonary hypertension induced by high pulmonary blood flow by down-regulating vasoactive peptides ET-1 and CTGF expressions in lung tissues of rats.     

Alteration of p38 MAPK activity in lung tissue in diabetic rats

AIM: To observe the pathologic changes in lung and the role of p38 MAPKinase signal pathways in pulmonary alteration in diabetic rats. METHODS: Diabetic rats were induced by intraperitoneally injected streptozotozin (STZ). After 4 weeks, we observed the pathologic changes in lungs, tested protein kinase C (PKC) activities by isotope in lungs of model rats, tested transforming growth factor (TGF-β₁) by Western blotting and immunohistochemical analysis, and determined the expression of p38 MAPKinase mRNA using in situ hybridization.RESULTS: After STZ administration for 4 weeks, we observed thickened pulmonary capillary basal lamina and increased number of fibre in Diabetes mellitus (DM) rats. TGF-β₁ levels, PKC and p38 MAPK activities were also found increased. CONCLUSION: The increased activities of TGF-β₁ and p38 MAPK suggeste that TGF-β₁ may play an important role in diabetic lung, and hyperglycemia-PKC-p38 MAPK signal pathways may be involved in the pathogenesis of diabetes.