CAJ | 학술논문

目的：观察糖肾宁对自发性2型糖尿病 KK-Ay 小鼠肾功能及肾组织降解酶系基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶组织抑制剂-1( tissue inhibitor of metalloproteinase 1,TIMP-1)蛋白及基因表达的影响。方法采用自发性2型糖尿病 KK-Ay 小鼠建立糖尿病肾病模型,随机分为模型组、缬沙坦组和糖肾宁组各20只,设立 C57BL/6J 小鼠20只为空白组；予通心络及缬沙坦干预12周后,测定各组小鼠血清尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,SCr),采用 Western Blot 、Realtime-PCR、免疫组化方法检测 MMP-9、TIMP-1蛋白表达或定位及基因表达水平。结果与空白组比较,模型组小鼠 BUN、SCr 均明显升高(P<0.05)；肾组织 TIMP-1蛋白及基因表达明显升高、MMP-9蛋白及基因表达明显降低(P<0.05)；与模型组比较,糖肾宁组和缬沙坦组 BUN、SCr 均明显降低(P<0.05),肾组织 TIMP-1蛋白及基因表达明显降低、MMP-9蛋白及基因表达明显升高(P<0.05)。结论糖肾宁能够保护自发性2型糖尿病 KK-Ay小鼠肾功能、延缓糖尿病肾病肾纤维化进展,调控糖尿病肾病肾组织降解酶系可能是糖肾宁防治糖尿病肾病的作用机制之一。
목적：관찰당신저대자발성2형당뇨병 KK-Ay 소서신공능급신조직강해매계기질금속단백매-9(matrix metalloproteinase-9,MMP-9)、기질금속단백매조직억제제-1( tissue inhibitor of metalloproteinase 1,TIMP-1)단백급기인표체적영향。방법채용자발성2형당뇨병 KK-Ay 소서건립당뇨병신병모형,수궤분위모형조、힐사탄조화당신저조각20지,설립 C57BL/6J 소서20지위공백조；여통심락급힐사탄간예12주후,측정각조소서혈청뇨소담(blood urea nitrogen,BUN)、혈청기항(serum creatinine,SCr),채용 Western Blot 、Realtime-PCR、면역조화방법검측 MMP-9、TIMP-1단백표체혹정위급기인표체수평。결과여공백조비교,모형조소서 BUN、SCr 균명현승고(P<0.05)；신조직 TIMP-1단백급기인표체명현승고、MMP-9단백급기인표체명현강저(P<0.05)；여모형조비교,당신저조화힐사탄조 BUN、SCr 균명현강저(P<0.05),신조직 TIMP-1단백급기인표체명현강저、MMP-9단백급기인표체명현승고(P<0.05)。결론당신저능구보호자발성2형당뇨병 KK-Ay소서신공능、연완당뇨병신병신섬유화진전,조공당뇨병신병신조직강해매계가능시당신저방치당뇨병신병적작용궤제지일。
[Abstract ]Objective To explore effects of Tangshenning on expression of matrix metalloproteinase-9 (MMP-9)、tissue inhibitor of metalloproteinase 1 ( TIMP-1) in diabetic nephropathy mice model. Methods Diabetic male KK-Ay mice were randomLy divided into three groups: the model group (n= 20),the valsartan group( n = 20) and the Tangshenning group ( n = 20). Male C57BL / 6J (n=20)mice were designed as the control group. After intervention with Tangshenning and valsartan for 12 weeks,serum creatinine (Scr) and serum urea nitrogen(BUN) were examined. Expression of MMP-9, TIMP-1 were accessed by Realtime-Pcr , Western Blot and Immunohistochemistry. Results Compared with control group, BUN and SCr were significantly increased (P<0. 05), while them of mice in valsartan and tangshenning group were decreased compared with model group(P<0. 05). Compared with the control group, the protein and gene expression of MMP9 and TIMP-1 both have the same trend in model group, the expression of MMP9 were decreased significantly and the expression of TIMP-1 were increased significantly (P<0. 05). Through the treatment of Tangshenning and valsartan for 12 weeks, the expression of TIMP-1 were down-regulated and the expression of MMP-9 were up-regulated in diabeticKK-Ay mice(P<0. 05). Conclusion Tangshenning could protect renal function and delay the process of renal fibrosis partly through regulating extracellular matrix degradation enzymes MMP-9 / TIMP-1 expression.