参芪扶正注射液对结肠癌小鼠恶液质后骨骼肌线粒体功能的影响

Effects of Shenqi Fuzheng Injection on function and dynamics of skeletal muscle mitochondria in mice after colon cancer-cachexia

目的 探讨结肠癌恶液质小鼠骨骼肌中线粒体功能变化及参芪扶正注射液干预后的影响。方法 将40只雌性BLAB/c裸鼠随机分为对照组、模型组及参芪扶正注射液低、高剂量组,每组10只。除对照组外,其余各组均ip人结肠癌Lovo细胞,并饲养至肿瘤广泛转移,制备癌症恶液质动物模型;根据消瘦程度和体质量变化监测各组小鼠癌症恶液质状态,ip给予参芪扶正注射液低、高剂量,每3天给药1次,连续给药7次。21 d后观察小鼠体质量变化,检测腓肠肌中三磷酸腺苷(ATP)、丙二醛(MDA)水平;Western blotting法检测小鼠腓肠肌中线粒体相关蛋白4-羟基壬烯酸(4HNE)、PPARγ共激活因子-1(PGC-1)、电压依赖型阴离子孔道蛋白(VDAC1)的表达情况。结果 与对照组比较,模型组与参芪扶正注射液干预组小鼠均出现癌症恶液质状态;与对照组比较,模型组小鼠腓肠肌ATP水平下降,MDA合成增多,腓肠肌线粒体相关蛋白4HNE和PGC-1表达水平均升高(P<0.05),VDAC1表达无明显差异;与模型组比较,参芪扶正注射液组小鼠腓肠肌ATP水平升高,MDA合成减少,腓肠肌线粒体相关蛋白4HNE和PGC-1表达水平均降低(P<0.05),VDAC1表达亦无明显差异。结论 参芪扶正注射液可以明显改善结肠癌腹腔转移小鼠的恶液质状态,可能与调节腓肠肌中线粒体功能、减轻线粒体氧化损伤有关。

Objective To study the changes of mitochondria function and dynamics in colon cancer-cachexia mice and the effects of Shenqi Fuzheng Injection on these changes.Methods A total of 40 female BLAB/c nu mice were randomly divided into control group,model group,low dose and high does of Shenqi Fuzheng Injection group,ten mice in every group.Except the control group,the mice of other groups were intraperitoneal injected with the Lovo cell line to establish the model of abdominal metastasis of colon cancer,then induced cancer cachexia.Marasmus and weight change were monitored the status of cancer cachexia in all groups.Shenqi Fuzheng Injection groups received intraperitoneal injection with 1.5 mL(2 times dose)and 3 mL(4 times dose)of drugs for every three days,seven consecutive times.After 21 days treatment,the mitochondrial related protein PGC-1,4HNE and VDAC1 in the skeletal muscle were measured.The levels of adenosine triphosphate(ATP)and malondialdehyde(MDA)in the skeletal were detected.Results Compared to the control group,the mice in the model group and Shenqi Fuzheng group suffered from cancer cachexia.Compared with the control group,the level of ATP in the skeletal muscle was lower in model group;The protein expression level of PGC-1 and 4HNE were remarkably increased(P<0.05);There was no significant difference in the protein expression of VDAC1(P>0.05);The level of MDA was significantly increased(P<0.05).After the treatment,compared with model group,the level of ATP in the skeletal muscle was higher;The protein expression levels of PGC-1 and 4HNE were significantly decreased(P<0.05);There was no significant difference in the protein expression of VDAC1(P>0.05);The level of MDA was lower(P<0.05).Conclusion Shenqi Fuzheng Injection can significantly improve the status of colon cancer cachexia in mice,which may be related to the improvement of the mitochondrial function and the relieving of the mitochondrial oxidative damage.