摘要
目的观察MMP-9/TIMP-1在糖尿病(DM)大鼠肾小管上皮细胞的表达,及缬沙坦对其影响。方法 30只雄性Wistar大鼠随机分为正常对照组(n=10),糖尿病模型组(n=10)和缬沙坦组(n=10)。采用腹腔内一次性注射STZ 55 mg/(kg.d)诱导糖尿病模型。缬沙坦组大鼠于糖尿病成模后给予缬沙坦30 mg/(kg.d)灌胃。分别于第8、16周末,每组随机处死5只大鼠,取肾组织HE和Masson染色观察肾小管间质病变;免疫组化法检测肾小管上皮细胞MMP-9、TIMP-1及TGF-β1的表达并作半定量分析。结果①与对照组比较,DM模型组大鼠肾小管间质病变显著加重,肾小管上皮细胞的TGF-β1、MMP-9、TIMP-1表达增强,但MMP-9/TIMP-1比值下降,其MMP-9与TIMP-1表达失调;②缬沙坦组大鼠上述改变的程度显著小于糖尿病模型组。结论①MMP-9/TIMP-1失衡可能是DM肾小管间质病变进展的一个因素;②缬沙坦可通过改善MMP-9/TIMP-1失衡,减轻肾小管间质病变。
【Objective】 To observe the effects of Valsartan on expression of MMP-9/TIMP-1 in renal tubular epithelial cells of diabetic nephropathy rats,elucidate the possible renal-protective mechanisms of Valsartan.【Methods】 Thirty male Wistar rats were randomly divided into 3 groups： normal control group（n =10）,diabetic model group（n =10）,and Valsartan treatment group（Valsartan 30 mg/kg·d,n =10）.Five rats of each group were killed respectively at 8,16 weeks.The pathologic change and expressions of ILK and MMP-9/TIMP-1 in renal tubular epithelial cells were detected.【Results】 Comparing with the control group,renal tubular-interstitial lesions in the diabetic model group is significantly aggravated,the TGF-β1,MMP-9,TIMP-1 expressions elevated while the MMP-9/TIMP-1 ratio declined.The changes mentioned above in the Valsartan treatment group is significantly smaller than in diabetic model rats.【Conclusions】 MMP-9/TIMP-1 imbalance is one possible factor in the progress of renal interstitial fibrosis in diabetes mellitus.Valsartan can improve the process of renal tubular-interstitial lesions by regulating MMP-9/TIMP-1 level.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2011年第8期942-946,共5页
China Journal of Modern Medicine
