抵挡汤早期干预调节MMPs/TIMPs平衡对2型糖尿病大鼠大血管纤维化的影响  

Early Intervention of Didang Decoction Regulating Balance of MMPs/TIMPs on Fibrosis in Type 2 Diabetic Rats

作　　者：任秋月[1] 刘鹏[1] 姚蓉飞 常柏[2] REN Qiuyue;LIU Peng;YAO Rongfei;CHANG Bai(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Medical University Chu Hsien-I Memorial Hospital,Tianjin 300134,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津医科大学朱宪彝纪念医院,天津300134

出　　处：《吉林中医药》2020年第8期1071-1075,共5页Jilin Journal of Chinese Medicine

基　　金：国家自然科学基金项目资助(81473622,81973614)。

摘　　要：目的观察抵挡汤早期干预改善2型糖尿病大鼠大血管病变纤维化的作用,探讨其机制。方法采用高脂饲料喂养联合链脲佐菌素(STZ)方法制备2型糖尿病大鼠模型,抵挡汤早期干预组、中期干预组、晚期干预组分别于成模前4周、成模时、成模后4周予抵挡汤灌胃,氨基胍组、吡格列酮组于成模时分别予氨基胍、吡格列酮灌胃,正常对照组予等剂量生理盐水灌胃,于24周结束。采用ELISA法检测各组大鼠血清中基质金属蛋白酶(MMPs)、基质金属蛋白酶组织抑制因子(TIMPs)蛋白表达。结果与糖尿病组相比,除抵挡汤晚期干预组外,各干预组MMPs蛋白表达增加,TIMPs表达降低(P<0.05),其中MMP-2、MMP-8、MMP-9增加程度以及TIMP-1、TIMP-2降低程度均以抵挡汤早期干预组最显著(P<0.05),MMP-9/TIMP-1、MMP-2/TIMP-2以抵挡汤早期干预组升高最显著(P<0.05)。结论抵挡汤早期干预可通过上调MMPs/TIMPs,改善细胞外基质合成分解失衡,延缓2型糖尿病大血管病变纤维化进展。Objective To observe the effect and mechanism of the early intervention with Didang decoction (DDD) on relieving the fibrosis of type 2 diabetic rats with macrovascular lesion.Methods Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet.The DDD-early group,middle group and the late intervention group were fed with DDD 4 weeks before,during,and 4 weeks after modeling,respectively,the aminoguanidine group and pioglitazone group received gavage of aminoguanidine and pioglitazone group,respectively,and the normal control group received normal saline until 24 weeks.The expression of Matrix metalloproteinase (MMPs) and Matrix metalloproteinase tissue inhibitor factor (TIMPs) in serum was detected by ELISA.Results Compared with the diabetes group,except for the late group,the expression of MMPs was increased and the expression of TIMPs was decreased in each intervention group (P<0.05),among which the increased degree of MMP-2,MMP-8 and MMP-9 and the decreased degree of TIMP-1 and TIMP-2 were most significant in the early group (P<0.05),the decrease of MMP-9/TIMP-1 and MMP-2/TIMP-2 in early group was the most significant (P<0.05).Conclusion Early intervention of DDD can improve the imbalance of extracellular matrix synthesis and delay the progression of Type 2 diabetic macroangiopathy by upregulating MMPs/TIMPs.

关 键 词：抵挡汤 2型糖尿病 大血管病变 纤维化 基质金属蛋白酶 基质金属蛋白酶组织抑制因子 

分 类 号：R289.9[医药卫生—方剂学]