丹参酚酸B对慢性肾炎大鼠的疗效及作用机制研究

Effectiveness and Mechanism of Salvianolic Acid B on Rats with Chronic Nephritis

目的观察丹参酚酸B对慢性肾炎模型大鼠的疗效,并探讨其作用机制。方法选取60只SD雄性大鼠,建立慢性肾炎模型,随机分为模型组、低、中及高剂量组各15只,另取15只大鼠作为对照组。低、中及高剂量组大鼠分别给予50、100和200 mg/kg丹参酚酸B灌胃,模型组和对照组给予相同体积的生理盐水灌胃。1周后,检测5组血肌酐(Scr)、血尿素(BUN)、血总胆固醇(TC)及24 h尿蛋白、血清丙二醛(MDA)、一氧化氮(NO)水平及超氧化物歧化酶(SOD)活性;处死大鼠,测定肾组织中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)和白介素-1β(IL-1β)mRNA水平及血清中蛋白水平,观察肾组织病理学变化。结果与模型组比较,低、中及高剂量组血Scr、血BUN、血TC、血清MDA、24 h尿蛋白水平下降,肾组织中TNF-α、IL-6和IL-1βmRNA和血清中蛋白水平下降,NO含量和SOD活性升高,且均呈剂量依赖性(P<0.05)。低、中及高剂量组肾组织病变程度随剂量增加而减轻。结论丹参酚酸B能改善慢性肾炎大鼠血Scr、血BUN、血TC及24 h尿蛋白水平,清除机体自由基,其机制可能与其抑制体内炎性因子水平相关。

Objective To observe effectiveness and mechanism of Salvianolic Acid B on rats with chronic ne-phritis. Methods A total of 60 SD male rats were established chronic nephritis models, and were randomly divided into model group, low-dose group, middle-dose group and high-dose group （ n=15 for each group） , and other 15 rats were selected as control group. Low-dose group, middle-dose group and high-dose group were respectively treated with 50 mg/kg, 100 mg/kg and 200 mg/kg Salvianolic Acid B by intragastric administration, while model and control groups were given equal volume of physiological saline by intragastric administration. One week after treatment, serum creatinine （Scr）, blood urea nitrogen （BUN）, serum total cholesterol （TC） and 24 h urine protein excretion levels, and serum malondialdehyde （ MDA） , nitric oxide （ NO） and superoxide dismutase （ SOD） activities were detected in the 5 groups. All rats were sacrificed, and then mRNA and protein levels of tumor necrosis factor alpha （ TNF-α） , Interleukin-6 （ IL-6） and Interleukin-1β （IL-1β） in nephridial tissues were detected, and pathological changes of nephridial tissues were observed. Results Compared with those in model group, Scr, BUN, serum TC, serum MDA and 24 h urine protein lev-els were significantly decreased;TNF-α, IL-6 and IL-1βmRNA and protein levels in nephridial tissues were significantly decreased, NO contents and SOD activities were significantly increased in low-dose, middle-dose and high-dose groups, and the changes had dose dependent （P〈0. 05）. Pathological changes were decreased with increasing dose in low-dose, middle-dose and high-dose groups. Conclusion Salvianolic Acid B may improve serum creatinine, blood urea nitrogen, blood total cholesterol and 24 h urine protein levels, and remove the body of free radicals, and its mechanism may be re-lated to its inhibition of inflammatory factors in vivo.