加味溺毒清合剂对单侧输尿管结扎大鼠肾间质纤维化的影响

Effects of Modified Niduqing Mixture on renal interstitial fibrosis in rats with unilateral ureteral obstruction

目的探讨加味溺毒清合剂治疗单侧输尿管结扎大鼠肾间质纤维化的机制。方法 SD雄性大鼠50只,除假手术组10只外,其余大鼠建立单侧输尿管结扎模型。造模后大鼠随机分为模型组、厄贝沙坦组、中药低剂量组、中药高剂量组,每组10只。分别采取相应的干预措施。检测尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG酶)、尿β_2微球蛋白(β_2-MG)、血肌酐(Scr)、血尿素氮(BUN)及肾组织中的转化生长因子β_1(TGF-β_1)和α-平滑肌肌动蛋白(α-SMA)的表达,并检查肾脏病理。结果 (1)尿β_2-MG含量:各组比较差异无统计学意义(P>0.05)。(2)尿NAG酶含量:14 d、28 d时模型组、中药低剂量组、中药高剂量组与假手术组比较均增高,差异有统计学意义(P<0.05);28 d时中药高剂量组与模型组比较明显减低,差异有统计学意义(P<0.05)。(3)血Scr水平:15 d时中药高剂量组与模型组、厄贝沙坦组比较降低并差异有统计学意义(P<0.05);29 d时,中药高剂量组与模型组比较,血Scr含量降低,差异有统计学意义(P<0.05);(4)血BUN水平:中药高剂量组与厄贝沙坦组比较,血BUN含量降低,差异有统计学意义(P<0.05)。29 d时,各组血BUN含量差异均无统计学意义(P>0.05)。(5)肾组织α-SMA、TGF-β_1表达:与假手术组比较,厄贝沙坦组、中药低剂量组、中药高剂量组、模型组差异有统计学意义(P<0.05);与模型组比较,厄贝沙坦组、中药低剂量组、中药高剂量组差异均有统计学意义(P<0.05)。结论加味溺毒清合剂能够降低尿NAG酶,同时通过抑制肾组织中α-SMA及TGF-β_1表达,从而减轻肾间质纤维化的程度。

Objective To explore the mechanism of Modified Niduqing Mixture on the renal interstitial fibrosis in rats with unilateral ureteral obstruction（ UUO）.Methods 50 male SD rats were selected.Except 10 rats in the sham-operation group,the UUO model was established in the other rats.After modeling,the rats were randomly divided into the model group,Erbesartan group,Chinese medicine groups with low-dose and high-dose,10 rats in each group.The rats were treated with the corresponding drugs.The urinary levels of N-acetyl β-D-Glucosaminidase（ NAG enzyme） and β2-microglobulin（ β2-MG）,the serum creatinine（ Scr）,blood urea nitrogen（ BUN）,and the expressions of transforming growth factor-β1（ TGF-β1） and α-smooth muscle actin（ α-SMA） in renal tissue were detected,and the renal pathology were observed.Results（1）There was no significant difference on the urinary β2-MG level among these groups（ P〉0.05）.（2）Compared with the sham-operation group,the urinary level of NAG on the 14 th day and 28 th day was increased significantly in the model group,Chinese medicine groups with low-and high-dose,with statistically significant differences（ P〈0.05）.The NAG level on the 28 th day in the high-dose group was decreased significantly compare with the model group（ P〈0.05）.（3）The Scr level on the 15 th day in the Chinese medicine group with high-dose was decreased significantly compared with the model group and Erbesartan group,with statistically significant differences（ P〈0.05）.The Scr level on the 29 th day in the Chinese medicine group with high-dose was significantly decreased compared with the model group,with statistically significant difference（ P〈0.05）.（4）Compared with the Erbesartan group,the BUN level was decreased in the Chinese medicine group with high-dose,with statistically significant difference（ P〈0.05）.There was no statistically significant difference on the BUN level among these groups on the 29 th day（ P〉0.05）.（5） Compared with the sham operation group,there were statistically significant differences on the expression levels of α-SMA and TGF-β1 in the model group,Erbesartan group and Chinese medicine groups with low-and high-dose（ P〈0.05）.Compared with the model group,there were also statistically significant differences on the expression levels of α-SMA and TGF-β1 in the Erbesartan group,Chinese medicine groups with low-and high-dose（ P〈0.05）.Conclusion Modified Niduqing Mixture can reduce the urinary NAG enzyme and inhibit the expressions of α-SMA and TGF-β1 in the renal tissue,thus alleviate the renal interstitial fibrosis.