灯盏花素对庆大霉素所致急性肾损伤的保护作用及机制研究

Protective effect and mechanism study of Breviscapine on acute kidney injury induced by gentamicin

关键词:  灯盏花素  肾损伤  庆大霉素  肾功能  炎症

Key words:  Breviscapine  kidney injury  gentamicin  renal function  inflammation

摘要:

[目的]研究灯盏花素（Bre）对庆大霉素所致大鼠急性肾损伤（AKI）的保护作用并探究其机制。[方法]取120只实验用Wistar大鼠随机分为正常对照组、模型对照组、肾炎康复片组[800 mg/（kg·d），阳性药对照组]、灯盏花素低[6 mg/（kg·d）]、中[12 mg/（kg·d）]、高[24 mg/（kg·d）]剂量组，每组20只；采用连续7 d腹腔注射庆大霉素制备AKI大鼠模型；各组均每天1次口服给药，疗程14 d，正常对照组和模型对照组均同步给予生理盐水。测定24 h排尿量并测定24 h尿蛋白量（Pro），测定尿N-乙酰-β-氨基葡萄糖苷酶（NAG酶）活性；测定血清尿素氮（BUN）、血肌酐（Scr）含量；称量肾脏质量并计算肾脏指数，免疫组织化学法法检测肾脏组织肾损伤分子-1（KIM-1）表达，苏木精-伊红（HE）染色法进行肾脏组织病理学检查并进行损伤评分，并测定肾脏组织氧化应激损伤指标和炎症细胞因子水平。[结果]与模型对照组比较，灯盏花素中、高剂量组和肾炎康复片组庆大霉素致AKI大鼠24 h排尿量、24 h Pro、尿NAG酶活性均显著降低（P<0.05或P<0.01）；血清BUN、Scr含量均显著降低，肾脏质量显著降低、肾脏指数显著减小，肾脏组织KIM-1表达降低，肾脏组织结构病变及细胞超微结构改变均明显改善，损伤评分显著降低，超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性升高且丙二醛（MDA）含量降低，肾脏组织巨噬细胞炎症蛋白-2（MIP-2）、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）含量降低；差异均具有统计学意义（P<0.05或P<0.01）。[结论]灯盏花素对庆大霉素致AKI大鼠肾组织损伤具有一定的保护作用，可能与其改善肾功能、抗氧化、抑制炎症有关。

Abstract:

[Objective] To investigate the protective effect of Breviscapine (Bre) on acute kidney injury (AKI) induced by gentamicin and its possible mechanism.[Methods] The 120 experimental Wistar rats were randomly divided into normal control group,model control group,Nephritis rehabilitation tablets group[800 mg/(kg·d),positive drug control group],Bre low-[75 mg/(kg·d)],medium-[150 mg/(kg·d)],high-[300 mg/(kg·d)] dose group,n=20;the AKI rat models were made by intraperitoneal injection of gentamicin. The drugs were continuously given for 14 days (once a day) and the rats in normal control group were given synchronous saline. Collecting and measuring 24-hour urine volume,and the activity of 24 h urine protein (Pro) and N-acetyl-β-glucosaminidase (NAG enzyme) were determined;the content of serum urea nitrogen (BUN),serum creatinine (Scr) were determined by biochemical analysis;the body weight,kidney weight were weighted and the kidney index was calculated;the expression of renal tissue damage-1 (KIM-1) was examined by immunohistochemical method (IHC). The pathological changes of renal tissue were observed by HE staining. The activities of oxidative stress index and inflammatory cytokines in renal tissue were measured.[Results] Compared with model control group,the 24 h urine output,24 h Pro of Bre medium-/high-dose groups and Nephritis rehabilitation tablets group were significantly decreased and the activity of NAG was significantly decreased(P<0.05 or P<0.01). The content of BUN,Scr was significantly decreased. The renal weight,renal index were significantly decreased;the expression of KIM-1 were down-regulated. Both of renal tissue structure lesions were significantly improved,the damage score were significantly reduced;the activity of SOD,CAT in renal tissue were significantly increased and the level of MDA were decreased;the content of MIP-2,MCP-1,TNF-α were significantly decreased;all of the difference above were significant (P<0.05 or P<0.01).[Conclusion] Bre has a protective effect on kidney injury induced by gentamicin in AKI rats,which may be related to alleviating renal tissue damage,anti-oxidation and inhibiting inflammation.