五味子多糖缓解顺铂诱导小鼠心功能不全与心脏炎症反应

Schisandra chinensis polysaccharide alleviates cisplatin-induced cardiac dysfunction and inflammation in mice

目的探讨五味子多糖(SCP)对顺铂诱导的小鼠心脏损伤与炎症反应的影响。方法将18只C57BL/6小鼠分为生理盐水组、顺铂组、顺铂+SCP组(SCP 20 mg/kg),单次腹腔注射顺铂3 mg/kg诱导小鼠心脏损伤,生理盐水组小鼠不给于顺铂诱导,注射顺铂前、后7 d顺铂+SCP组小鼠给予灌胃SCP处理,其余两组小鼠给予灌胃1%羧甲基纤维素钠溶液处理。通过超高分辨率小动物超声成像系统检测心功能;处死小鼠取心脏组织,采用实时荧光定量PCR(RT-qPCR)检测白细胞介素(IL)-6、肿瘤坏死因子-α(TNF-α)、高迁移率族蛋白1(HMGB1)和IL-1β的mRNA表达水平;苏木素-伊红(HE)和免疫组织化学染色分别观察心脏形态变化和TNF-α表达情况;试剂盒检测血清乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)水平;Western blot检测心肌组织核因子κB(NF-κB)及其磷酸化水平。结果相较与生理盐水组,顺铂组小鼠血清LDH与CK-MB水平升高,心肌组织纤维杂乱而不连续,炎症因子(IL-6、TNF-α、HMGB1和IL-1β)mRNA及磷酸化NF-κB(p-NF-κB)表达水平升高,小鼠出现心功能不全[心脏射血分数(EF)与缩短分数(FS)下降];与顺铂组比较,顺铂+SCP组小鼠血清LDH与CK-MB水平下降,心肌组织纤维有序而连续,炎症因子(IL-6、TNF-α、HMGB1和IL-1β)mRNA及p-NF-κB表达水平下降,小鼠心功能得到改善(EF与FS升高)。结论SCP能有效缓解顺铂诱导的小鼠心功能不全与炎症反应。

Objective To investigate the effect of Schisandra chinensis polysaccharide(SCP)on cisplatin-induced cardiac injury and inflammatory response in mice.Methods A total of 18 C57BL/6 mice were divided into the normal saline group,cisplatin group,cisplatin+SCP(20 mg/kg)group.Single intraperitoneal injection of cisplatin(3 mg/kg)induced cardiac injury in mice.Mice in the normal saline group were not induced by cisplatin,mice in the cisplatin+SCP group were given intragastric administration of SCP 7 d before and 7 d after the injection of cisplatin,and mice in the other two groups were given 1%sodium carboxymethyl cellulose solution by gavage.Cardiac function of mice was detected by ultra-high resolution ultrasound imaging system for small animals.The mice were sacrificed,and then the heart tissues were collected.The mRNA expression levels of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),high mobility group box 1 protein(HMGB1)and IL-1βwere detected by real-time quantitative PCR(RT-qPCR).Hematoxylin-eosin(HE)and immunohistochemical staining were used to observe cardiac morphological changes and detect TNF-αexpression,respectively.Serum lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)levels were detected by biochemical kits.The levels of nuclear factor(NF-κB)and its phosphorylation in myocardial tissues were detected by using Western blot.Results Compared with the normal saline group,the levels of serum LDH and CK-MB of mice in the cisplatin group were increased,the myocardial fibers were disordered and discontinuous,and the expression levels of inflammatory factors(IL-6,TNF-α,HMGB1 and IL-1β)mRNA and phosphorylated NF-κB(p-NF-κB)were increased,resulting in cardiac dysfunction,manifested as decreased heart ejection fraction(EF)and fractional shortening(FS).Compared with the cisplatin group,the levels of serum LDH and CK-MB of mice in the cisplatin+SCP group decreased,the myocardial fibers were ordered and continuous,the levels of inflammatory factors(IL-6,TNF-α,HMGB1 and IL-1β)mRNA and p-NF-κB decreased,and the cardiac function of mice was improved,manifested as increased EF and FS.Conclusion SCP can effectively alleviate cisplatin-induced cardiac dysfunction and inflammation response in mice.