黄芪多糖对CLP诱导的脓毒症小鼠急性肝损伤MDA、caspase-3和ICAM-1的影响研究

Effects of astragalus polysaccharides on MDA，caspase-3 and ICAM-1 in mice with sepsis-induced acute hepatic injury

摘要:

目的：探讨黄芪多糖（astragalus polysaccharide，ＡＰＳ）对脓毒症诱导的小鼠急性肝损伤丙二醛（methane dicarboxylic aldehyde，MDA）、半胱氨酸天冬氨酸蛋白酶-3（caspase-3）和细胞间黏附分子-1（intercellular adhesion molecule-1，ICAM-1）的影响。方法：将小鼠随机分为假手术组（SHAM组，n=25）、脓毒症组（SEP组，n=25）、APS处理组（APS组，n=25）、生理盐水处理组（NS组，n=25），采用盲肠结扎穿刺术（cecal ligation puncture，CLP）造模，APS组经腹腔注射APS 50 mg/（kg?d），NS组经腹腔注射等量生理盐水，SHAM组和SEP组不做特殊处理。染色观察肝脏组织病理变化；检测①血浆中MDA、caspase-3和ICAM-1变化；②肝组织匀浆MDA和caspase-3变化；③肝脏组织中caspase-3蛋白的表达。结果：SEP组12 h开始表现肝细胞水肿进行性加重，48 h达到高峰。APS干预后，肝细胞损害严重程度较SEP组明显改善。通过APS处理后，24、48 h APS组血浆中MDA[（29.69±4.62） mol/ml，P=0.041；（23.95±4.10） mol/ml，P=0.003]、caspase-3[（33.12±9.01） ?滋mol/L，P=0.000；（31.25±8.68） ?滋mol/L，P=0.000]和ICAM-1[（439.49±71.66） ?滋g/L，P=0.009；（321.87±68.64） ?滋g/L，P=0.000]浓度降低，肝组织匀浆MDA与caspase-3浓度亦在相应时相点开始降低。24、48 h APS组caspase-3蛋白[（19.93±4.53） ?滋mol/L，P=0.005；（16.91±4.76） ?滋mol/L，P=0.000]表达较SEP组明显降低。结论：APS可有效减轻急性肝损伤，其作用可能与降低MDA、ICAM-1以及抑制caspase-3表达有关。

Abstract:

Objective：To investigate the effects of astragalus polysaccharides on methane dicarboxylic aldehyde（MDA），caspase-3 and intercellular adhesion molecule -1（ICAM-1） in mice with sepsis-induced acute hepatic injury by cecal ligation puncture（CLP）. Methods：The mice were randomly divided into sham group（SHAM group，n=25），sepsis group（SEP group，n=25），APS treatment group（APS group，n=25） and saline -treated group（NS group，n=25）. Mouse model of acute hepatic injury was copied by CLP. The mice in APS group were injected with APS at a dosage of 50 mg/（kg?d）；no special treatment was made in SEP group and SHAM group；the mice in NS group was injected with equal volume of normal saline. Pathological changes in liver tissues were observed by staining. MDA，caspase-3 and ICAM-1 changes in plasma and liver homogenates，and the expression of caspase-3 in liver tissues were detected. Results：In SEP group，hepatocyte swelling began to show progressive increase at 12 h and peaked at 48 h. The severity of liver damage improved significantly in APS than in SEP group. The concentration of MDA（（29.69±4.62） mol/ml，P=0.041；（23.95±4.10） mol/ml，P=0.003），caspase-3（（33.12±9.01） ?滋mol/L，P=0.000；（31.25±8.68） ?滋mol/L，P=0.000） and ICAM-1（（439.49±71.66） ?滋g/L，P=0.009；（321.87±68.64） ?滋g/L，P=0.000） in plasma of APS group decreased at 24 h and 48 h，after treat－ment by APS. The concentration of MDA and caspase-3 in liver homo-genates also began to decrease in the corresponding time points. The expression of caspase-3（（19.93±4.53） ?滋mol/L，P=0.005（16.91±4.76） ?滋mol/L，P=0.000） in liver tissue of APS group was sig－nificantly lower than that in SEP group at 24 h and 48 h. Conclusion：Acute hepatic injury can be reduced by APS；its effect may be associated with the decreased expression of MDA，ICAM-1and caspase-3.