三黄益肾胶囊对糖尿病大鼠肾脏MMP-9及TNF-α表达的影响

Effect of Sanhuang Yishen Capsule on expression of MMP-9 and TNF-α in kidney of diabetic rats

目的观察三黄益肾胶囊对糖尿病大鼠肾脏组织中基质金属蛋白酶-9(MMP-9)及肿瘤坏死因子-α(TNF-α)表达的影响。方法从60只健康成年雄性Wistar大鼠中随机选10只作为正常对照组,余50只采用链脲佐菌素腹腔注射法制作糖尿病大鼠模型。将造模成功40只大鼠随机分为模型组、三黄益肾胶囊低剂量组、三黄益肾胶囊中剂量组、三黄益肾胶囊高剂量组,每组10只。三黄益肾胶囊低、中、高剂量组分别给予三黄益肾胶囊0.4 g/(kg·d)、0.8 g/(kg·d)、1.6 g/(kg·d)灌胃,正常组和模型组给予同等剂量生理盐水灌胃,均每日1次,连续8周。检测空腹血糖、肌酐、尿素氮、24 h尿蛋白定量,计算肾质量/体质量比值,并采用免疫组化法检测大鼠肾组织中MMP-9及TNF-α表达情况。结果各造模组血清BUN、SCr及UPro水平和肾质量/体质量比值均明显高于正常对照组(P均<0.05),三黄益肾胶囊中、高剂量组血清BUN、SCr及UPro水平和肾质量/体质量比值均明显低于模型组和三黄益肾胶囊低剂量组(P均<0.05);三黄益肾胶囊中、高剂量组肾组织中MMP-9表达量均明显高于模型组和三黄益肾胶囊低剂量组(P均<0.05),TNF-α表达量均明显低于模型组和三黄益肾胶囊低剂量组(P均<0.05)。结论三黄益肾胶囊能够通过抑制MMP-9在肾脏表达的下降及降低TNF-α在肾脏的表达,从而发挥延缓糖尿病大鼠肾损伤的作用。

Objective It is to observe the effect of Sanhuang Yishen Capsule on MMP-9 and TNF-α in the kidney of diabetic rats. Methods Sixty healthy adult male Wistar rats were selected, in which 10 rats as normal control group, the other 50 rats were used to establish diabetic rat models induced by intraperitoneal injection of streptozotocin. The successful models （n = 40） were randomly divided into model group, low, medium and high dose of Sanhuang Yishen Capsule groups with 10 rats in each group and were respectively given 0.4, 0.8, 1.6 g/（ kg · d） Sanhuang Yishen Capsule by intragastric administration, normal group and model group were given the same volume of normal saline at the same time. Every group was treated once per day and for 8 weeks. Fasting blood glucose, creatinine, blood urea nitrogen （BUN）, 24 hour urinary protein were determined and renal heavy/body weight index was calculated, and the expression of MMP-9 and TNF-α in renal tissue of the rats was detected by immunohistochemical method. Results The serum levels of BUN, SCr, UPro and renal heavy/body weight ratio in every modeling group were higher than that in normal group （ P 〈 0.05 ） , and these indexes in medium and high dose of Sanhuang Yishen capsule groups were significantly lower than that in model group and low dose of Sanhuang Yishen capsule group （P 〈 0.05 ）. The expression of MMP-9 in renal tissue in medium and high dose of Sanhuang Yishen capsule groups was signif- icantly higher while the expression of TNF-α were significantly lower than that in model group and low dose of Sanhuang Yishen capsule group （ P 〈 0.05 ）. Conclusion Sanhuang Yishen Capsule can delay the development of renal injury in diabetic rats by inhibiting the decrease of expression of MMP-9 and increase of expression of TNF-α in renal tissue.