糖代谢异常大鼠肝组织中内质网应激相关分子CHOP和Caspase-12的表达变化  

Changes of endoplasmic reticulum stress-related molecules CHOP and Caspase-12 in liver tissues of rats with abnormal glucose metabolism

作　　者：樊林花[1] 李丹[2] 刘茂林[1] 卫兵艳[1] 王春芳[1] 刘田福[1] 刘建新 

机构地区：[1]山西医科大学实验动物中心实验动物和人类疾病动物模型山西省重点实验室,太原030001 [2]山西医科大学第二临床医学院肿瘤生物治疗科 [3]山西省一O九医院

出　　处：《山西医科大学学报》2015年第4期297-300,385,共5页Journal of Shanxi Medical University

基　　金：山西省实验动物专项基金资助项目(2013k11);山西医科大学科技创新基金资助项目(01201425)

摘　　要：目的观察高脂饮食诱导的糖代谢异常大鼠肝脏糖原沉积与内质网应激(ERS)相关分子CCAAT/增强子结合蛋白同源蛋白(CHOP)和半胱氨酸天冬氨酸蛋白酶12(Caspase-12)在肝脏中的表达变化。方法 SD雄性大鼠60只,随机分为糖耐量受损组(IGT,n=20),IGT对照组(n=10),2型糖尿病组(T2DM,n=20)及T2DM对照组(n=10)。采用高脂饮食饲养12周诱导IGT大鼠,高脂饮食饲养4周后腹腔注射链脲佐菌素诱导T2DM大鼠。过碘酸雪夫氏(PAS)染色观察各组大鼠肝脏糖原改变;real-time PCR技术检测肝脏组织中CHOP mRNA的表达;Western blot技术检测肝脏组织中Caspase-12蛋白的表达。结果 IGT组和T2DM组大鼠肝脏糖原含量丰富。IGT组和T2DM组肝组织CHOP mRNA的表达水平与各自对照组相比,差异无统计学意义(P>0.05),而Caspase-12蛋白表达水平明显升高(P<0.01);与IGT组相比,T2DM组Caspase-12蛋白表达水平明显降低(P<0.01)。结论糖代谢异常大鼠肝组织糖原含量明显增多,ERS相关分子Caspase-12表达水平增高,肝组织中存在内质网应激,肝糖原沉积可能是内质网应激的诱因之一。Objective To observe the deposition of hepatic glycogen and changes of liver endoplasmic reticulum stress-related mole- cules CCAAT/enhancer binding protein homologous protein （CHOP）and acid cysteine aspartie acid protein 12 （Caspase-12） in rats with abnormal glucose metabolism induced by high-fat diet. Methods Sixty male Sprague-Dawley rats were randomly divided into four groups ： impaired glucose tolerance （IGT） group （ n = 20）, IGT control group （ n = 10）, type 2 diabetes mellitus （ T2DM ） group （ n = 20 ） and T2DM control group（ n = 10 ）. IGT rats were induced by feeding high-fat diet for 12 weeks, and T2DM rats were produced by feeding high-fat diet for 4 weeks and intraperitoneally injecting streptozolocin. Changes of hepatic glycogen were observed after PAS staining. The expression of CHOP mRNA in liver tissues was detected by real-time PCR. The expression of Caspase-12 protein in liver tissue was determined by Western blot. Results The content of hepatic glycogen was rich in IGT group and T2DM group. Compared to the corresponding control groups, the expression of CHOP mRNA in IGT group and T2DM group had no significant differenee（P 〉 0.05 ）. The expression of Caspase-12 protein in IGT group and T2DM group was significantly higher than those in the corresponding control groups （P 〈 0.01 ）. Compared to IGT group, the expression of Caspase-12 protein was markedly decreased in T2DM group （ P 〈 0.01 ）. Cortclusion The content of hepatic glycogen increases obviously in rats with abnormal glucose metabolism ,the expression of Caspase-12 is up-regulated ,and the endoplasmic reticulum stress exists in the liver. The deposition of hepatic glycogen may be one of the factors of endoplasmie reticulum stress.

关 键 词：内质网应激 CCAAT/增强子结合蛋白同源蛋白 半胱氨酸天冬氨酸蛋白酶12 糖耐量受损 2型糖尿病 

分 类 号：R587.1[医药卫生—内分泌]