丁基苯酞缓解高脂喂养诱导的大鼠心肌炎性损伤的实验研究

Experimental study of 3-n-butylphthalide alleviating myocardial inflammatory injury induced by high fat feeding in rats

目的探讨丁基苯酞(NBP)在肥胖诱导的心脏炎症反应及心肌损伤中的保护作用。方法15只SD大鼠随机分为三组,每组5只。正常组给予正常饮食,模型组及NBP组大鼠给予高脂饲料饮食。高脂喂养8周后,NBP组给予大鼠NBP(40 mg/kg·d)灌胃治疗。16周后处死大鼠,检测大鼠血脂水平;运用Western Blot、RT-PCR、组织染色和免疫组化检测大鼠心脏结构、各项病理情况以及相关信号通路蛋白和基因的表达。结果组织病理显示模型组较正常组大鼠心肌肌丝紊乱(HE染色)、间质纤维化(Masson染色)的严重程度均更明显,NBP组上述改变较模型组均缓解。高脂喂养16周后,相比于正常组,模型组大鼠心肌组织中的肥厚标志基因心房利钠肽(ANP)及脑钠肽(BNP)水平升高,抗凋亡蛋白B淋巴细胞瘤-2(Bcl-2)表达下调,凋亡相关蛋白Bcl-2相关蛋白X(Bax)表达上调,心肌组织炎症因子肿瘤坏死因子(TNF)-α及炎症细胞标志物CD68的含量均升高,炎症信号蛋白核因子κB(NF-κB)抑制蛋白α(IκB-α)的含量降低,炎症相关基因的mRNA水平升高,氧化应激标志蛋白3-硝基酪氨酸(NT)的含量升高,差异有统计学意义(均P<0.05);NBP组上述改变较模型组均缓解(均P<0.05)。结论NBP在肥胖相关的心肌损伤中具有治疗效果,且这些作用主要得益于其抗炎作用。

Objective To investigate the protective effects of N-Butylphthalide(NBP)on cardiac inflammatory response and myocardial injury induced by obesity.Methods Fifteen SD rats were randomly divided into three groups with 5 rats in each group.Normal group was given normal diet,model group and NBP group were given high fat diet.After 8 weeks of high fat feeding,NBP group was given NBP(40 mg/kg·d)intragastric treatment.After 16 weeks,the rats were sacrificed to detect blood lipid levels.Western Blot,RT-PCR,tissue staining and immunohistochemistry were used to detect the cardiac structure,pathological conditions and the expression of proteins and genes in related signaling pathways.Results Histopathology showed that the severity of myocardial filaments disorder(HE staining)and interstitial fibrosis(Masson staining)were more obvious in model group than in normal group,and the above changes were alleviated in NBP group compared with model group.After 16 weeks of high fat feeding,compared with normal group,the levels of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)increased in model group,the expression of anti-apoptotic protein B lymphocytoma-2(Bcl-2)was down-regulated and apoptotic related protein Bcl-2(Bax)was upregulated;the contents of inflammatory factor tumor necrosis factor-αand inflammatory cell marker CD68 in myocardial tissue increased,the content of inflammatory signaling protein nuclear factorκB inhibitory proteinα(IκB-α)decreased,the mRNA level of inflammation-related genes increased,and the content of oxidative stress marker protein 3-nitrotyrosine(NT)increased;the differences were statistically significant(P<0.05).The above changes were alleviated in NBP group,compared with model group(P<0.05).Conclusion NBP has therapeutic effects on obesity-related myocardial injury,and these effects are mainly due to its anti-inflammatory effect.