摘要
目的:研究丹参酮Ⅱ_A(TSⅡ_A)磺酸钠注射液对万古霉素(VAN)致肾损伤模型大鼠的保护作用及其机制。方法:将72只大鼠随机分为空白组、模型组、阳性对照组(氨磷汀,1 mg/kg)和TSⅡ_A磺酸钠注射液低、中、高剂量组(15、30、60μg/kg),每组12只。除空白组外,其余各组大鼠均于尾iv VAN(200 mg/kg)复制肾损伤模型,造模成功后给药组大鼠每天ip相应药物1次,空白组和模型组大鼠ig生理盐水,连续10 d。测定大鼠尿中24 h蛋白量及N-乙酰-β-D氨基葡萄糖苷酶(NAG)、人肾损伤因子1(KIM-1)水平,测定血清中胱抑素C(CysC)、肌酐(Scr)、尿素氮(BUN)和肾组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮(NO)水平,并观察肾组织的病理变化。结果:与空白组比较,模型组大鼠血清中CysC、Scr、BUN水平,尿中24 h蛋白量和NAG、KIM-1水平以及肾组织中MDA、NO水平均明显升高,肾组织中SOD、GSH-Px水平明显降低(P<0.01);病理结果显示,模型组大鼠发生肾小管浊肿、刷状缘脱落,肾小管上皮细胞崩解、脱落等肾损伤病变。与模型组比较,各给药组大鼠血清中CysC、Scr、BUN水平,尿中24 h蛋白量和NAG、KIM-1水平,以及肾组织中MDA、NO水平均明显降低,且肾组织中SOD、GSH-Px水平明显升高(P<0.05或P<0.01);肾脏的病理变化明显减轻。结论:TSⅡ_A磺酸钠注射液能有效改善VAN所致大鼠肾损伤,其机制可能与抑制大鼠体内的氧化反应有关。
OBJECTIVE:To study the protective effect of tanshinone Ⅱ_A (TSⅡ_A )sulfonate injection against vancomycin(VAN)-induced renal injury model rats and its mechanism. METHODS:72 rats were randomly divided into blank group,model group,positive control group(amifostine,1 mg/kg)and TSⅡ_A sulfonate injection low-dose,medium-dose and high-dose groups(15,30,60 μg/kg),with 12 rats in each group. Except for blank group,those groups were given VAN(200 mg/kg)intravenously via tail vein to induce renal injury rat model;after modeling,each drug group was given relevant medicine intraperitoneally once a day,and blank group and model group were given normal saline intragastrically for consecutive 10 days. The levels of 24 h protein,NAG and KIM-1 in urine were determined,and those of Cys C,Scr and BUN in serum and those of SOD,MDA,GSH-Px and NO in renal homogenate were also determined;the pathological change of renal tissue was observed. RESULTS:Compared with blank group,the levels of Cys C,Scr and BUN in serum,those of 24 h protein,NAG and KIM-1 in urine and those of MDA and NO in renal tissue increased significantly in model group,while the levels of SOD and GSH-Px decreased significantly(P〈0.01);the pathological slice indicated that model group suffered from renal injury such as kidney tubules albuminoid degeneration,brush border abscission,renal tubular epithelial cell disintegration and abscission. Compared with model group,the levels of CysC,Scr and BUN in serum,those of 24 h protein,NAG and KIM-1 in urine and those of MDA and NO in renal tissue decreased significantly in treatment groups,while the levels of SOD and GSH-Px in renal tissue increased significantly(P〈0.05 or P〈0.01);pathological changes of renal tissue were relieved significantly. CONCLUSIONS:TS Ⅱ_A sulfonate injection can effectively relieve VAN-induced renal injury in rats,and its mechanism may be associated with inhibiting the oxidative reaction of rats in vivo.
出处
《中国药房》
CAS
北大核心
2016年第22期3081-3084,共4页
China Pharmacy