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丹参酮Ⅱ对急性肾衰竭大鼠的保护作用

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目的 探讨丹参酮Ⅱ对急性肾衰竭大鼠的保护作用及其分子机制.方法 45只SD大鼠按照随机数字表法分对照组、肾衰组和丹参酮组,肾衰组和丹参酮组大鼠腹腔注射10 mg/kg脂多糖建立急性肾衰竭大鼠模型,对照组注射等体积生理盐水.建模成功后,丹参酮组大鼠腹腔注射30 mg/kg丹参酮Ⅱ,对照组和肾衰组大鼠注射等体积生理盐水.治疗7 d后,采用苏木精-伊红染色分析3组大鼠肾脏病理学变化;检测3组大鼠血清肌酐(Scr)、尿酸(UA)、胱抑素C(Cys C)和血尿氮水平(BUN);采用原位缺口末端标记法(TUNEL)染色分析肾组织细胞凋亡水平;采用酶联免疫吸附实验分析3组大鼠血清炎性因子水平;采用蛋白质免疫印迹分析蛋白激酶B(Akt)/磷脂酰肌醇3激酶(PI3K)、半胱氨酰天冬氨酸特异性蛋白酶-3(Caspase-3)和B细胞淋巴瘤/白血病-2相关X蛋白(bax)蛋白表达水平.组间计量数据比较采用单因素方差分析.结果 丹参酮组大鼠肾脏组织病理评分[(1.27±0.70)分]低于肾衰组[(3.13±0.74)分],差异用统计学意义(t=15.100,P<0.05).丹参酮组大鼠血清 Scr、血 BUN、UA 和 CysC[(0.76±0.09)μmol/L、(72.20±12.73)mmol/L、(232.93±18.66)μmol/L、(0.33±0.05)mg/L]低于肾衰组[(1.22±0.08)µmol/L、(118.00±19.87)mmol/L、(375.53±28.20)μmol/L、(0.49±0.06)mg/L],差异有统计学意义(t=15.260、7.516、8.048、16.330,P<0.05).丹参酮组大鼠血清白细胞介素-6和肿瘤坏死因子[(70.07±7.76)、(55.67±10.73)ng/ml]低于肾衰组[(130.60±20.79)、(85.33±8.36)ng/ml],差异有统计学意义(t=10.560、8.443,P<0.05).丹参酮组大鼠肾脏组织凋亡指数[(14.02±1.98)%]低于肾衰组[(33.30±6.67)%],差异用统计学意义(t=10.730,P<0.05).丹参酮组大鼠肾脏组织磷酸化Akt和磷酸化PI3K蛋白表达水平(0.83±0.07、0.80±0.06)高于肾衰组(0.57±0.09、0.44±0.11),差异有统计学意义(t=11.750、12.630,P<0.05).丹参酮组大鼠肾脏组织Caspase-3和bax蛋白表达水平(0.70±0.07、0.76±0.08)低于肾衰组(0.99±0.10、1.19±0.08],差异有统计学意义(t=9.468、14.030,P<0.05).结论 丹参酮Ⅱ对脂多糖诱导的急性肾衰竭具有保护作用,降低炎性反应和细胞凋亡,主要依赖于Akt/PI3K信号通路.
Protective effect of tanshinone Ⅱ on rats with acute renal failure
Objective To investigate the protective effect of tanshinone Ⅱ on acute renal failure rats and its molecular mechanism.Methods 45 SD rats were randomly divided into control group,renal failure group and tanshinone group by random number table method(10 mice/group).The rats in renal failure group and tanshinone group were injected with 10 mg/kg lipopolysaccharide intritoneally to establish acute renal failure rat model,and the rats in control group were injected with equal volume normal saline.After successful modeling,the rats in the tanshinone group were intraperitoneally injected with 30 mg/kg tanshinone Ⅱ,and the rats in the control group and the renal failure group were injected with equal volume normal saline.After 7 days of treatment,hematoxylin-eosin staining was used to analyze renal pathological changes in the three groups.Serum creatinine(Scr),uric acid(UA),cystatin C(Cys C)and blood and urine nitrogen(BUN)levels were detected in the three groups.The apoptosis level of renal tissue was ana-lyzed by terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)staining.Serum in-flammatory factors were analyzed by enzyme-linked immunosorbent assay(ELISA).The expression levels of protein kinase B(Akt)/phosphatidylinositol 3 kinase(PI3K),cysteinyl aspartate-specific protease-3(Caspase-3)and B cell lymphoma/leukemia-2 associated X protein(bax)were analyzed by Western blot-ting.One-way analysis of variance was used to compare the measurement data between groups.Results The pathological score of kidney tissue in tanshinone group[(1.27±0.70)points]was significantly lower than that in renal failure group[(3.13±0.74)points],and the difference was statistically significant(t=15.100,P<0.05).Scr,BUN,UA and Cys C in tanshinone group[(0.76±0.09)μmol/L,(72.20±12.73)mmol/L,(232.93±18.66)μmol/L,(0.33±0.05)mg/L]was lower than that in group renal failure rats[(1.22±0.08)μmol/L,(118.00±19.87)mmol/L,(375.53±28.20)μmol/L,(0.49±0.06)mg/L,t=15.260,7.516,8.048,16.330,P<0.05].Serum interleukin-6 and tumor necrosis factor[(70.07±7.76),(55.67±10.73)ng/ml]in tanshinone group were significantly lower than those in renal failure group[(130.60±20.79),(85.33±8.36)ng/ml,t=10.560,8.443,P<0.05].The apoptosis index of renal tissue in tanshinone group[(14.02±1.98)%]was significantly lower than that in renal failure group[(33.30±6.67)%,t=10.730,P<0.05].The protein expression levels of phospho-rylated Akt and phosphorylated PI3K in the renal tissue of rats in the tanshinone group(0.83±0.07,0.80±0.06)were significantly higher than those in the renal failure group(0.57±0.09,0.44±0.11,t=11.750 12.630,P<0.05).The protein expression levels of Caspase-3 and bax in the renal tissue rats in the tanshinone group(0.70±0.07,0.76±0.08)were significantly than those in the renal failure group(0.99±0.10,1.19±0.08,t=9.468,14.030,P<0.05).Conclusion Danshensu Ⅱ has a protective effect on acute renal failure induced by lipopolysaccharide,reducing inflammatory response and cell apopto-sis,mainly through the Akt/PI3K signaling pathway.

Tanshinone ⅡAcute renal failureInflammationApoptosis

任松涛、文秀华、赵强、王焕东

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黄淮学院附属医院(驻马店市中心医院)急诊科,驻马店 463000

黄淮学院附属医院(驻马店市中心医院)泌尿外科,驻马店 463000

河南省胸科医院急诊科,郑州 453000

丹参酮Ⅱ 急性肾衰竭 炎症 凋亡

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(12)