摘要
目的观察临床用于降糖治疗的噻唑烷二酮类药物吡格列酮对大鼠缺血再灌注损伤心肌的保护作用及对p38丝裂原活化蛋白激酶表达的影响。方法将24只健康雄性SD大鼠随机分为4组:假手术组(Sham组)、缺血再灌注组(I/R组)、吡格列酮10mg/(kg·d)组(P组)、吡格列酮10mg/(kg·d)+过氧化物酶体增殖物激活受体γ(PPARγ)特异性阻断剂GW9662组(P+G组),每组6只;利用结扎左前降支的方法建立缺血再灌注损伤模型,脱氧核糖核苷酸末端转移酶介导的缺口原位末端标记法检测心肌细胞凋亡,Western blot方法检测心肌组织磷酸化p38(p-p38)蛋白的变化。结果与I/R组比较,Sham组、P组心肌细胞凋亡指数(AI)显著降低[(8.6±4.3)%、(21.4±8.8)%vs(40.1±12.3)%,P<0.05];P+G组心肌细胞AI显著高于P组[(37.0±10.5)%vs(21.4±8.8)%,P<0.05]。与I/R组比较,Sham组、P组p-p38蛋白表达下调,差异有统计学意义(P<0.05),与P组比较,P+G组p-p38蛋白表达上调,差异有统计学意义(P<0.05)。结论吡格列酮抑制缺血再灌注损伤诱导的心肌细胞凋亡,可能与下调p-p38表达有关,这2种作用是由PPARγ介导的。
Objective To study the effect of pioglitazone,a member of the thiazolidinedione （TZD） class with hypoglycemic action to treat diabetes, on expression of p38 mitogen-activated protein kinase in myocardium of rats following I/R injury. Methods Twenty-four healthy SD rats were randomly divided into sham group, I/R injury group, pioglitazone treatment group and pioglitazone＋peroxisome proliferator-activated receptors-y specific antagonist GW9662 treatment group （6 in each group）. A rat I/R injury model was established by ligating the left anterior descending coronary artery. Apoptosis of myocardial cells was assayed by Terminal dUTP deoxynucleotidyltransferase nick end-labeling. Expression of p-p38 protein was detected by Western blot. Results The apoptosis index of myocardial cells was significantly lower in sham operation group and pioglitazone treatment group than in I/R injury group and was significantly higher in pioglitazone＋ GW9662 treatment group than in pioglitazone treatment group （8.6%±4.3%,21.4%±8.8% vs 40.1%±12.3% ,P〈0.05,37.0%±10.5% vs 21.4%±8.8%,P〈0. 05）. The expression level of p-p38 was significantly lower in sham operation group and pioglitazone treatment group than in I/R injury group and was significantly higher in pioglitazone＋GW9662 treatment group than in pioglitazone treatment group （P〈0.05）. Conclusion Pioglitazone can inhibit I/R injury-induced apoptosis of myocardial cells by downregulating the expression of p-p38 protein.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2018年第2期188-190,共3页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
解放军总医院临床科研扶持基金(2015FC-TSYS-2017)
