解聚复肾宁对糖尿病大鼠肾脏PKC、PDGF-β、VEGF和BMP-7的作用研究
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摘要
目的:观察中药复方解聚复肾宁(JJFSN)对糖尿病(DM)大鼠肾脏PKC(蛋白激酶C)、VEGF(血管内皮生长因子)和PDGF-β(血小板衍化生长因子β)和BMP-7(骨形成蛋白7)的影响并探讨其对肾脏的保护作用机制。方法:建立STZ诱导的糖尿病SD大鼠模型,将成模糖尿病大鼠随机分成4组:模型组、JJFSN组、厄贝沙坦组、JJFSN+厄贝沙坦组,同时设正常对照组。各组大鼠采用相应的干预措施处理12周。常规方法检测各组大鼠肾重/体重、血糖、尿素氮、血肌酐、尿白蛋白排泄率(UAER);免疫组化法检测肾组织PKC、VEGF和BMP-7的表达,Western blot检测肾组织PDGF-B的表达。光镜观察肾脏病理改变。结果:模型组肾脏病理改变明显,血糖、UAER、尿素氮、血肌酐、肾指数显著增高,肾皮质PKC、VEGF和PDGF-β表达显著升高,而肾组织BMP-7表达显著减少;JJFSN组、厄贝沙坦组和JJFSN+厄贝沙坦组血糖、UAER、尿素氮、血肌酐、肾指数及肾组织PKC、VEGF和PDGF-β等指标显著低于模型组(P<0.05),而肾组织BMP-7表达显著高于模型组(P<0.05),肾脏病理改变明显改善;JJFSN+厄贝沙坦组上述各项指标改善明显优于模型组、JJFSN组和厄贝沙坦组(P<0.05),但未达到正常对照组水平。结论:JJFSN对DM大鼠肾脏形态和功能有明显保护作用,其机制可能与减少肾组织中PKC、VEGF和PDGF-β的表达并增加DM大鼠肾组织中BMP-7的表达。
Objective:To investigate the effect of Jiejufushenning(JJFSN) on expression of renal protein kinase C(PKC),renal vascular endothelial growth factor(VEGF),renal platelet-derived growth factorβ(PDGF-β) and renal bone morphogenetic protein-7(BMP-7) in diabetic nephropathy rats and evaluate the protective effects of Jiejufushenning(JJFSN) on renal lesion in diabetic rats.Methods:The diabetic SD rats induced by STZ were divided into four groups: diabetic control group, Jiejufushenning group,Irbesartan group and Jiejufushenning combined with Irbesartan group,and the normal control group. After experimental rats in every group were respectively treated for 12 weeks by above intervention methods.The relative kidney weight, blood sugar,urea nitrogen, serum creatinine, and urinary albumin excretion rate (UAER) were detected by routine analysis methods, and PKC、VEGF and BMP-7 in renal tissue was detected by immunohistochemical techniques,and PDGF-βin renal tissue was detected by Western blot,and pathologic variation of kidney was observed by microscope.Results:The expression of renal PKC、VEGF and PDGF-βwas increased in diabetic rats . The expression of renal BMP-7 was decreased in diabetic rats.The pathologic variation of kidney was noticeably changed, and the blood sugar,UAER,urea nitrogen,serum creatinine and relative kidney weight were significantly increased in diabetic rats. While in addition to the expression of renal BMP-7 ,the above indexes in JJFSN group,Irbesartan group and JJFSN combined with Irbesartan group were significantly lower than in diabetic control group (P<0.05), the expression of renal cortex BMP-7 in JJFSN group, Irbesartan group and JJFSN combined with Irbesartan group were significantly higher than in diabetic control group(P<0.05), and pathologic variation of kidney was improved,and the improvement of all indexes in JJFSN combined with Irbesartan group was most significant (P<0.05). Conclusion:JJFSN has the protective effects on renal lesion in diabetic rats. The mechanism of the protective effects of JJFSN on renal lesion may be downregulating the expression of PKC、VEGF and PDGF-β,and increasing the level of BMP-7 in the renal tissue.
Objective:To investigate the effect of Jiejufushenning(JJFSN) on expression of renal protein kinase C(PKC),renal vascular endothelial growth factor(VEGF),renal platelet-derived growth factorβ(PDGF-β) and renal bone morphogenetic protein-7(BMP-7) in diabetic nephropathy rats and evaluate the protective effects of Jiejufushenning(JJFSN) on renal lesion in diabetic rats.Methods:The diabetic SD rats induced by STZ were divided into four groups: diabetic control group, Jiejufushenning group,Irbesartan group and Jiejufushenning combined with Irbesartan group,and the normal control group. After experimental rats in every group were respectively treated for 12 weeks by above intervention methods.The relative kidney weight, blood sugar,urea nitrogen, serum creatinine, and urinary albumin excretion rate (UAER) were detected by routine analysis methods, and PKC、VEGF and BMP-7 in renal tissue was detected by immunohistochemical techniques,and PDGF-βin renal tissue was detected by Western blot,and pathologic variation of kidney was observed by microscope.Results:The expression of renal PKC、VEGF and PDGF-βwas increased in diabetic rats . The expression of renal BMP-7 was decreased in diabetic rats.The pathologic variation of kidney was noticeably changed, and the blood sugar,UAER,urea nitrogen,serum creatinine and relative kidney weight were significantly increased in diabetic rats. While in addition to the expression of renal BMP-7 ,the above indexes in JJFSN group,Irbesartan group and JJFSN combined with Irbesartan group were significantly lower than in diabetic control group (P<0.05), the expression of renal cortex BMP-7 in JJFSN group, Irbesartan group and JJFSN combined with Irbesartan group were significantly higher than in diabetic control group(P<0.05), and pathologic variation of kidney was improved,and the improvement of all indexes in JJFSN combined with Irbesartan group was most significant (P<0.05). Conclusion:JJFSN has the protective effects on renal lesion in diabetic rats. The mechanism of the protective effects of JJFSN on renal lesion may be downregulating the expression of PKC、VEGF and PDGF-β,and increasing the level of BMP-7 in the renal tissue.
引文
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