复方钩藤降压片对自发性高血压大鼠肾动脉超微结构及MMP-2/TIMP-2、MMP-9/TIMP-1的影响

Effects of Compound Uncaria hypotensive tablet on renal artery ultrastructure and MMP-2/TIMP-2,MMP-9/TIMP-1 in SHR

目的探讨复方钩藤降压片(又名天苓降压片)对自发性高血压大鼠(SHR)肾动脉超微结构及血管重塑标志物的的影响。方法SHR随机分为模型组(M组)、厄贝沙坦片组(Y组)、复方钩藤降压片组(S组),每组10只,另设10只WKY大鼠为正常对照组(C组),给药6周,透射电镜观察大鼠肾动脉超微结构;免疫组化法检测肾动脉中MMP-2、9及TIMP-1、2的蛋白表达情况。结果镜下复方钩藤降压片组大鼠肾动脉中层平滑肌细胞体积有所缩小,形状较为规则,分布较为均匀,核膜偶有皱缩现象,胞质内可见较为完整的线粒体,少量的粗面内质网存在轻微扩张、水肿;细胞外基质及胶原纤维减少;动脉壁弹力膜厚薄较为均匀,无断裂部位;血管内皮细胞体积明显缩小,与内膜连接较为紧密,细胞质中的线粒体未见明显的肿胀,嵴线较为清晰,细胞核减小,未见呈呈高柱状突入血管管腔的内皮细胞。免疫组化显示与模型组比较,复方钩藤降压片组大鼠MMP-2/9蛋白表达均降低,而相应的抑制酶TIMP-1/2蛋白表达升高。结论复方钩藤降压片具有改善肾动脉血管重塑作用,其机制与调节肾动脉基质金属蛋白酶及其抑制酶的浓度和比值趋于正常有关。

Objective To investigate the effects of Compound Uncaria hypotensive tablet on renal artery ultrastructure and vascu-lar remodeling markers in spontaneously hypertensive rats(SHR).Methods SHRs was randomly divided into model group(Group M),irbesartan tablet group(GroupY)and Compound Uncaria hypotensive tablet group(Group S),with 10 rats in each group and 10 WKY rats as normal control group(Group C),after 6 weeks of administration,the ultrastructure of rat renal artery was observed by transmission electron microscope;the protein expression of MMP-2,9 and TIMP-1,2 in renal artery were de-tected by immunohistochemical.Results Under microscope,the volume of middle smooth muscle cells in renal artery in Com-pound Uncaria hypotensive tablet group was reduced,the shape was regular,the distribution was more uniform,the nuclear mem-brane was occasionally shrunk,and relatively complete smooth muscle cells were seen in cytoplasm Mitochondria,a small amount of rough endoplasmic reticulum with slight expansion and edema;Extracellular matrix and collagen fibers decreased;The thick-ness of elastic membrane of arterial wall was uniform without fracture;The volume of vascular endothelial cells was significantly reduced and connected closely with the intima.There was no obvious swelling of mitochondria in the cytoplasm,the ridge line was clear,the nucleus was reduced,and there were no endothelial cells protruding into the vascular lumen in a high columnar shape.Immunohistochemistry showed that compared with the model group,the expression of MMP-2/9 protein decreased and the ex-pression of TIMP-1/2 protein increased in the Compound Uncaria hypotensive tablet group.Conclusion Compound Uncaria hy-potensive tablet can improve renal artery vascular remodeling,and its mechanism is related to regulating the concentration and ra-tio of renal artery matrix metalloproteinase and its inhibitor.