摘要
目的探究利拉鲁肽对链脲霉素致糖尿病大鼠心肌损伤的保护作用机制。方法60只SD大鼠中随机取12只作为空白对照组,其余48只大鼠随机分为模型组和低、中、高剂量利拉鲁肽组。采用一次性腹腔注射链脲霉素(55 mg/kg)诱导糖尿病大鼠模型,造模前7 d皮下注射低、中、高剂量的利拉鲁肽(35μg/kg、70μg/kg、140μg/kg),1次/d,连续注射7 d。空白对照组和模型组以等量生理盐水替代。处理结束后,检测大鼠心功能指标[左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、射血分数(EF),短轴缩短率(FS)]和空腹血糖水平。HE染色和Masson染色观察大鼠心肌损伤和纤维化程度;酶联免疫吸附(ELISA)法检测大鼠血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)的含量;Western blot检测Toll样受体4(TLR4)、髓样分化蛋白(MyD88)及核因子κB P65(NF-κB P65)表达。结果与空白对照组相比,模型组大鼠LVESD、LVEDD、空腹血糖、CVF、TNF-α、IL-1β、IL-6、TLR4、MyD88及NF-κB P65磷酸化水平明显升高,EF、FS明显降低(P<0.05),心肌病理损伤显著增加。与模型组相比,利拉鲁肽处理组LVESD、LVEDD、空腹血糖、CVF、TNF-α、IL-1β、IL-6、TLR4、MyD88及NF-κB P65磷酸化水平明显降低,EF、FS明显升高(P<0.05),心肌病理损伤明显减轻。结论利拉鲁肽可呈剂量依赖性地降低大鼠血糖水平,保护糖尿病大鼠心肌损伤,抑制TLR4/MyD88/NF-κB活化后介导的炎症反应可能是其作用机制。
Objective To explore protective effect mechanism of liraglutide on myocardial injury in rats with streptozotocin(STZ)induced diabetes mellitus(DM).Methods Twelve of the 60 SD rats were randomly selected as the blank control group,and the remaining 48 rats were randomly divided into the model group and the low,medium and high dose liraglutide groups.One-time intraperitoneal injection of STZ(55 mg/kg)was conducted to induce DM rat models.At 7 d before modeling,low,medium and high dose of liraglutide(35μg/kg,70μg/kg,140μg/kg)was subcutaneously injected,once/d for continuous 7 d.The blank control group and the model group were replaced with an equal amount of physiological saline.At the end of treatment,cardiac function indexes[left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),ejection fraction(EF),fractional shortening(FS)]and level of fasting blood glucose were detected.The myocardial injury and fibrosis degree were observed by HE staining and Masson staining.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were detected by ELISA.Western blot was applied to detect expression of Toll-like receptor4(TLR4),myeloid differentiated protein(My D88)and nuclear factorκB P65(NF-κB P65).Results Compared with the blank control group,LVESD,LVEDD,fasting blood glucose,CVF,TNF-α,IL-1β,IL-6,TLR4,My D88 and NF-κB P65 phosphorylation level were significantly increased in model group,while EF and FS were significantly decreased(P<0.05),and myocardial pathological damage was significantly increased.Compared with model group,LVESD,LVEDD,fasting blood glucose,CVF,TNF-α,IL-1β,IL-6,TLR4,MyD88 and NF-κB P65 phosphorylation level were significantly decreased in liraglutide treatment group,while EF and FS were significantly increased(P<0.05),and myocardial pathological damage was significantly alleviated.Conclusion Liraglutide can reduce blood glucose level of rats,protect myocardial injury of DMrats.Inhibit TLR4/My D88/NF-κB activation and alleviating inflammatory response may be action mechanism.
作者
刘金岩
王斌
王燕
LIU Jin-yan;WANG Bin;WANG Yan(Department of Pharmacy,People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi Xinjiang 830001,China)
出处
《临床和实验医学杂志》
2020年第1期26-30,共5页
Journal of Clinical and Experimental Medicine
基金
新疆维吾尔自治区自然科学基金资助项目(No.2015211C246)
