虫草菌丝对糖尿病大鼠肾组织中基质金属蛋白酶2及其组织抑制因子2表达的影响

Effect of cordycepic hypha on expressions of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in kidney of different time diabetic rats

目的观察虫草菌丝(CS)对糖尿病(DM)大鼠肾脏病理及肾组织中基质金属蛋白酶(MMP)-2和基质金属蛋白酶组织抑制因子(TIMP)-2表达的影响,探讨CS的肾脏保护作用及其可能机制。方法应用链脲佐菌素(STZ)诱导DM大鼠模型,随机分为DM模型组、CS干预组1、2。同时设阴性对照组。干预组1成模后即予CS5.0g·kg-1.d-1进行干预,干预组2在成模4w后开始予等量CS。8w后测定各组血糖、血尿素氮(BUN)、血肌酐(Scr)、24h尿蛋白定量(Upro)等变化。光镜观察肾组织病理变化。用免疫组化法检测肾组织MMP-2、TIMP-2、Ⅳ胶原(ColⅣ)蛋白的表达。结果与阴性对照组相比,其他3组大鼠血糖、BUN、Scr、Upro均显著上升(均P<0.01);肾组织中MMP-2蛋白表达降低(P<0.01),TIMP-2蛋白表达升高,ColⅣ表达亦增加(P<0.01)。与DM模型组相比,CS干预后,上述异常指标除血糖外均有明显改善(P<0.05或P<0.01),除血糖及BUN外干预组1优于干预组2(P<0.05或P<0.01)。结论CS对DM大鼠具有保护肾脏组织、改善肾脏功能的作用。其作用机制可能与上调肾组织MMP-2的表达和下调TIMP-2的表达,从而减轻肾小球细胞外基质沉积有关;且治疗越早,疗效越好。

Objective To observe the effects of cordycepic hypha （cordyceps sinensis, CS） on the pathological changes, the expres- sion 6f matrix metalloproteinase （MMP）-2 and tissue inhibitor of metalloproteinase （TIMP）-2 in nephridial tissue of diabetic nephropathy （DN） rats and to explore the protective effects of CS and its mechanisms on the kidney. Methods Diabetic rat models were induced by injection of streptozotocin （STZ）. These rats were randomly divided into diabetes model,CS1 （5.0 g·kg^-1·d^-1 ,given at the onset of DM model） and CS2 （5.0 g·kg^-1·d^-1,given after 4 w） groups. At the same time,negative control group was set up. Plasma glucose,serum creatinine （SCr） ,blood urea nitrogen （BUN） ,and 24 h urinary protein （Upro） were observed after 8 weeks. The pathological changes of kid- ney were observed by light microscopy. The expressions of MMP-2, TIMP-2 and Col Ⅳ were detected in nephridial tissue by immunohistochemical technique. Results Compared with negative control group, the other three groups had significantly higher plasma glucose, Scr, BUN and Upro levels（ all P 〈 0. 01 ） ; MMP-2 expression was decreased significantly in nepbridial tissues （P 〈 0. 01 ）, but Col Ⅳ as well as TLMP- 2 expressions increased （P 〈 0. 01 ）. After interfered, compared with DM model group, the above-mentioned abnormal indexes were improved significantly （ P 〈 0. 05 or P 〈 0. 01 ）, except for plasma glucose. CS1 group had better effect than CS2 （ P 〈 0. 05 or P 〈 0. 01 ）, except for plasma glucose and BUN. Conclusions CS has some protective effect on the kidney of diabetic rats,which may be related with the inhibition of excessive deposition of glomeruli extracellular matrix by up-regulating MMP-2 and downregnlating TIMP-2 expressions. And the earlier treatment, the better effect.