CAJ | 학술논문

目的：探讨沉默信息调节因子2相关酶1/核转录因子-κB（Sirt1/NF-κB）信号通路在抗肿瘤药阿霉素诱导的心肌损伤中的作用及瑞舒伐他汀钙的干预效果。 　　方法：将30只4~6周龄雄性C57BL/6J小鼠随机分为对照组、模型组和干预组，每组各10只。干预组预先给予瑞舒伐他汀钙稀释灌胃7天后，干预组和模型组分别给予阿霉素15 mg/kg腹腔注射建立心肌损伤模型，建模后干预组继续瑞舒伐他汀干预5天，同时模型组与对照组给予等量生理盐水灌胃。12天后，处死全部小鼠取心脏组织，多聚甲醛固定，经石蜡包埋、切片、苏木精-伊红（HE）染色后，观察各组小鼠心肌病理变化；取心肌组织匀浆检测氧化应激指标丙二醛（MDA）含量、超氧化物歧化酶（SOD）活力；免疫组化法测各组小鼠心肌Sirt1/NF-κB表达水平。 　　结果：与对照组相比，模型组心肌匀浆MDA含量、心肌组织NF-κB水平均明显升高，匀浆SOD活力、心肌组织Sirt1水平均显著降低（P<0.05），差异均有统计学意义，且心肌结构紊乱、炎症细胞浸润明显；与模型组比较，干预组MDA含量、NF-κB水平均明显下降但仍高于对照组，匀浆SOD活力、心肌Sirt1水平均升高（P<0.05），差异有统计学意义，且心肌结构完整、细胞水肿及淋巴浸润明显减少。 　　结论：Sirt1/NF-κB信号通路参与了阿霉素诱导的心肌损伤过程，瑞舒伐他汀能通过上调该信号通路保护阿霉素所致的心肌毒性损伤。
목적：탐토침묵신식조절인자2상관매1/핵전록인자-κB（Sirt1/NF-κB）신호통로재항종류약아매소유도적심기손상중적작용급서서벌타정개적간예효과。 　　방법：장30지4~6주령웅성C57BL/6J소서수궤분위대조조、모형조화간예조，매조각10지。간예조예선급여서서벌타정개희석관위7천후，간예조화모형조분별급여아매소15 mg/kg복강주사건립심기손상모형，건모후간예조계속서서벌타정간예5천，동시모형조여대조조급여등량생리염수관위。12천후，처사전부소서취심장조직，다취갑철고정，경석사포매、절편、소목정-이홍（HE）염색후，관찰각조소서심기병리변화；취심기조직균장검측양화응격지표병이철（MDA）함량、초양화물기화매（SOD）활력；면역조화법측각조소서심기Sirt1/NF-κB표체수평。 　　결과：여대조조상비，모형조심기균장MDA함량、심기조직NF-κB수평균명현승고，균장SOD활력、심기조직Sirt1수평균현저강저（P<0.05），차이균유통계학의의，차심기결구문란、염증세포침윤명현；여모형조비교，간예조MDA함량、NF-κB수평균명현하강단잉고우대조조，균장SOD활력、심기Sirt1수평균승고（P<0.05），차이유통계학의의，차심기결구완정、세포수종급림파침윤명현감소。 　　결론：Sirt1/NF-κB신호통로삼여료아매소유도적심기손상과정，서서벌타정능통과상조해신호통로보호아매소소치적심기독성손상。
Objective: To investigate the effects of rosuvastatin for up-regulating the expression of Sirt1/NF-κB signal pathway and inhibiting doxorubicin (DOX)-induced cardiotoxicity injury in experimental mice. Methods: A total of 30 male C57 BL/6J mice at (4-6) weeks of age were randomly divided into 3 groups. Treatment group, the mice received intra-gastric rosuvastatin for 7 days, followed by intra-peritoneal injection of DOX 15mg/kg to induce the cardiotoxicity injury, and then received rosuvastatin for another 5 days. Model group, the mice received intra-peritoneal injection of DOX 15mg/kg to induce the cardiotoxicity injury, and then received intra-gastric normal saline for the same volume. Control group, the mice received intra-gastric normal saline for the same volume. n=10 in each group. The mice were killed at 12 days after treatment. The pathological change in myocardial tissue was observed by HE staining, the myocardial oxidative stress indexes of malonadehyde (MDA) level and super oxide dismutase (SOD) activity were measure by the operating kits and the protein expression of Sirt1/NF-κB was examined by immunohistochemistry. Results: Compared with Control group, Model group had obviously increased levels of MDA, NF-κB and decreased SOD activity, Sirt1 level, all P<0.05;the mice in Model group showed disordered myocardial structure with inlfammatory cell inifltration. Compared with Model group, Treatment group had obviously decreased levels of MDA, NF-κB (while they were still higher than Control group), and increased SOD activity, Sirt1 level, all P<0.05;the mice in Treatment group showed intact myocardial structure with much less edema and lymphocyte inifltration. Conclusion: Sirt1/NF-κB signal pathway was involved in DOX-induced cardiotoxicity injury in experimental mice, rosuvastatin could protect the injury via up-regulating the expression of Sirt1/NF-κB signal pathway.