维药昆仑雪菊多糖对四氯化碳所致小鼠急性肝损伤的预防作用及机制研究

摘要

目的:研究维药昆仑雪菊多糖(KSCP)对四氯化碳(CCl4)所致小鼠急性肝损伤的预防作用及机制.方法:将96只小鼠随机分为正常组(生理盐水)、模型组(生理盐水)、联苯双酯滴丸组(阳性对照,1.5 mg/10 g)和KSCP低、中、高剂量组(0.3、0.6、1.2 mg/10 g),每组16只,ig给药,每天1次,连续10 d.除正常组外,其余各组小鼠均ip 1%CCl4菜籽油溶液诱导肝损伤.造模24 h后,检测各组小鼠血清中谷氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肿瘤坏死因子α(TNF-α)、白细胞介素1(IL-1)的水平和肝组织中丙二醛(MDA)、超氧化物歧化物(SOD)的水平,计算小鼠肝、脾指数,观察肝组织病理变化并进行病理评分,检测肝组织中凋亡相关基因Caspase-3、Bcl-2、Bax蛋白表达.结果:与正常组比较,模型组小鼠血清中ALT、AST、TNF-α、IL-1水平和肝组织中MDA水平以及肝、肾指数均明显升高(P<0.01),肝组织中SOD水平明显降低(P<0.01);肝组织发生肝细胞坏死、变性和炎症细胞浸润等病理变化,病理评分明显增加(P<0.01);肝组织中Caspase-3蛋白表达水平以及Bcl-2/Bax比值均明显降低(P<0.01).与模型组比较,各给药组小鼠上述指标均明显改善(P<0.05或P<0.01).结论:KSCP对CCl4所致小鼠急性肝损伤有一定预防作用,其机制可能与抗氧化、抗炎及调节凋亡相关蛋白的表达有关.%OBJECTIVE:To study the preventive effect and mechanism of Wei medicine Kunlun snow chrysanthemum polysac-charides(KSCP)on carbon tetrachloride(CCl4)-induced acute liver injury in mice. METHODS:96 mice were randomly divided in-to normal group(normal saline),model group(normal saline),Biphenyl diester dropping pill(positive control,1.5 mg/10 g)and KSCP low-dose,medium-dose,high-dose groups (0.3,0.6,1.2 mg/10 g),16 in each group,with intragastric administration, once a day,for 10 d. Except for normal group,mice in other groups were intraperitoneally injected 1%CCl4 rapeseed oil solution to induce liver injury. After 24 h of modeling,the levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),tu-mor necrosis factor α(TNF-α),interleukin 1(IL-1)in serum,levels of malondialdehyde(MDA),superoxide dismutase(SOD) in liver tissue were detected;the liver,spleen indexes were calculated. Pathological changes of liver tissue were observed,patho-logical scoring was conducted. The protein expressions of apoptosis-related genes Caspase-3,Bcl-2,Bax in liver tissue were detect-ed. RESULTS:Compared with normal group,levels of ALT,AST,TNF-α,IL-1 in serum,MDA level in liver tissue and liver, spleen indexes in model group were obviously increased(P<0.01);SOD level in liver tissue was decreased(P<0.01);pathologi-cal changes in hepatocellular necrosis,degeneration and inflammatory cell infiltration,and pathological score in model group was obviously increased(P<0.01);caspase-3 protein expression and Bcl-2/Bax ratio in liver tissue in model group were obviously de-creased (P<0.01). Compared with model group,above-mentioned indexes in each administration group were obviously improved (P<0.05 or P<0.01). CONCLUSIONS:KSCP has certain preventive effect on CCl4-induced acute liver injury in mice,and its mechanism may be associated with anti-oxidation,anti-inflammation and regulation of apoptosis-related protein expressions.