银杏叶提取物对糖尿病大鼠肾脏基质金属蛋白酶2表达的影响

Effect of ginkgo biloba extract on the expression of matrix metalloproteinase-2 in diabetic nephropathy rats

目的 观察银杏叶提取物（GbE）对雄性SD糖尿病大鼠肾脏基质金属蛋白酶2（MMP-2）和Ⅳ型胶原表达的影响,从而探讨银杏叶对糖尿病肾病的保护机制.方法 24只链脲佐菌素诱导的SD大鼠完全随机分成糖尿病对照组（DM组）和GbE组,并以12只正常雄性SD大鼠作为正常对照组（NC组）.分别于4、8周后,观察各组大鼠体重、肾重、随机血糖、尿蛋白排泄率等生化指标,并用免疫组化和逆转录聚合酶链反应方法 观察糖尿病大鼠肾脏MMP-2及Ⅳ型胶原的表达.结果 糖尿病大鼠的随机血糖、体重、肾脏/体重明显下降,尿白蛋白排泄率明显升高[DM组（31.59±4.59）mg/24 h比NC组（8.74±2.08）mg/24 h,P＜0.05],GbE组糖尿病大鼠尿白蛋白排泄率[（21.38±3.86）mg/24 h]较DM组有所下降（P＜0.05）.8周时,与正常对照组相比,DM组大鼠肾小球MMP-2蛋白的表达水平明显下降[（0.49±0.07）mg/24 h比（0.15±0.04）mg/24 h,P＜0.05],而GbE组DM组大鼠肾小球MMP-2蛋白的表达水平[（0.48±0.07）mg/24 h]较DM组无明显下降（P＞0.05）;DM组大鼠Ⅳ型胶原的表达水平较NC组明显升高[（3.48±0.54）mg/24h比（1.68±0.51）mg/24 h],而GbE组糖尿病大鼠较NC组无明显升高[（2.55±0.50）mg/24 h比（1.68±0.51）mg/24 h].结论 GbE可通过抑制糖尿病大鼠MMP-2过表达,进而对糖尿病肾病发挥保护作用.

Objective To study the effect of ginkgo biloba extract （GbE） on the expression of matrix metalloproteinase （MMP）-2 in kidneys of diabetic rates and to analyze the protecting mechanism of GbE on diabetic nephropathy. Methods Totally 24 SD rats of diabetic nephropathy induced by streptozotocin were randomly divided into two groups： diabetes group and treatment group with GbE, and 12 rats with placebo therapy were enrolled as the normal control group. Rats were killed after 4 ～ 8 weeks treatment and the expression of MMP-2 and type Ⅳ collagen were studies by immunohistochemistry and RT-PCR. Results In diabetic rats, blood sugar, weight and kidney/body weight ratio were decreased significantly and the excretion of 24 hour urinary protein was increased significantly compared to the diabetes group. But the excretion of 24 hour urinary protein was improved in GbE group （ P 〈0.05 ）. The expression level of MMP-2 protein and mRNA was decreased significantly in renal glomduri of diabetic rats （ P 〈 0.05 ） but showed no changes in GbE treatment group compared to diabetes group（ P 〉 0.05 ）. The expression level of type Ⅳ collagen was significantly increased in diabetic rats（ P 〈0.05 ） but showed no changes in GbE group（ P 〉0.05）. Conclusion GbE can improve diabetic nephropathy by inhibiting the expression of MMP-2 in diabetic Rat.