脉血康对单侧输尿管梗阻大鼠肾保护作用及机制探讨

Protective effect of Maixuekang on renal function in rats with unilateral ureteral obstruction and its underlying mechanism

目的观察脉血康对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾脏保护作用并探讨其可能作用机制。方法建立UUO大鼠模型,大鼠随机分为假手术组、模型组及脉血康组3组,各组给予相应干预,各组大鼠于术后14 d处死,抽取血清并留取肾组织标本,检测各组大鼠血肌酐(SCr)、尿素氮(BUN)、胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)情况,并观察各组肾脏病理改变情况,采用免疫组化方法观察肾组织中组织型纤溶酶原激活物(tissue type plasminogen activator,t-PA)、尿激酶型纤溶酶原激活物(urokinase type plasminogen activator,u-PA)、纤溶酶原激活物抑制剂1(plasminogen activator inhibitor-1,PAI-1)在各组的表达情况。结果①3组肾脏形态学变化有差异,假手术组双肾大小及体积无改变,颜色红润,模型组及脉血康组术侧肾脏体积明显增大,术侧肾盂肾盏及输尿管结扎段以上全程扩张。模型组肾实质颜色变浅,剖面肾皮质变薄,皮髓质分界不清,脉血康组肾脏颜色稍红润,肾脏皮髓质分界较清。②假手术组肾脏病理未见明显改变,与假手术组比较,模型组及脉血康组肾小管损伤及肾间质纤维化程度显著(P<0.01);与模型组比较,脉血康组肾小管损伤及肾间质纤维化程度明显减轻(P<0.05)。③与假手术组相比,模型组SCr、BUN、TC、TG水平均升高(P<0.05),与模型组相比,脉血康组SCr、BUN、TC、TG水平均下降(P<0.05)。④假手术组PAI-1、t-PA、u-PA表达于肾小管上皮细胞及肾小球系膜细胞胞浆,肾间质表达极少;与假手术组比较,模型组及脉血康组PAI-1明显增多(P<0.05),而t-PA、u-PA表达明显减少(P<0.05),与模型组相比,脉血康组PAI--1表达明显减少,t-PA表达明显增多(P<0.05),u-PA无明显差别(P>0.05)。结论脉血康可能通过调节脂质代谢下调肾脏PAI-1的表达,上调t-PA的表达从而促进肾脏细胞外基质降解,对UUO大鼠肾间质纤维化及肾功能具有保护作用。

Objective To observe the protective effect of Maixuekang on renal function in rats with unilateral ureteral obstruction （UUO）, and to investigate the possible mechanism. Methods UUO model was established. Rats were divided into three groups., sham operation group, model group and Maixuekang group. Corresponding intervention was given in each group, and rats of each group were sacrificed at 14th day after operation. Serum and renal tissue samples were obtained for determination of serum creatinine （SCr）, blood urea nitrogen （BUN）, cholesterol （TC）, triglyceride （TG） levels, ob- servation of the renal tissue pathological changes in different groups, and detection of the expression of tissue type plasminogen activator （t-PA）, urokinase type plasminogen activator （u-PA）, and plasmino- gen activator inhibitor-I （PAl-1） in the renal tissue by immunohistochemistry. Results （1） There was significant difference among the three groups in the morphological changes of kidney. The size and vol- ume of the kidney in sham operation group had no change, and the color was red. The renal volume in model group and Maixuekang group was significantly increased, and renal pelvis and renal calyx on the affected side were expanded. In model group, the color of the kidney become lighter, the kidney cortex became thinner, and the boundary of cortex and medulla were not clear. The renal color in Maixuekang group was slightly red, and the boundary of the renal cortex and medulla was clear. （2） There was no obvious change in renal pathology in sham operation group. Renal tubular injury and renal interstitial fi- brosis （RIF） were significantly increased in model group and Maixuekang group as compared with sham operation group （P〈0. 01 ）, and those were significantly decreased in Maixuekang group as compared with model group （P〈0. 05）. （3） As compared with sham operation group, SCr, BUN, TC and TG levels were elevated in model group （P〈0.05）, and those were decreased in Maixuekang group as com- pared with those in model group （P〈0.05）. （4） t-PA, u-PA and PAI-1 were expressed in renal tubu- lar epithelial cells and glomerular mesangial cells, and those were rarely seen in the renal interstitia in sham operation group. As compared with sham operation group, the expression of PAI-1 was signifi- cantly increased （P〈0.05）, and the t-PA and u-PA expression decreased significantly （P〈0. 05） in the other two groups. As compared with model group, the expression of PAI-1 was significantly de- creased, and t-PA was significantly increased （P〈0. 05）, and u-PA had no significant change （P〈 0. 05） in Maixuekang group. Conclusions Maixuekang promoted the degradation of extracellular matrix of kidney by regulating lipid metabolism, down-regulating the expression of PAI-1, up-regulating the ex- pression of t-PA, and protected the RIF and renal function in UUO rats.