白细胞介素-22对高脂饮食诱导的ApoE^-/-小鼠主动脉内质网应激的影响  

Effects of interleukin-22 on aortic endoplasmic reticulum stress induced by high-fat diet in ApoE^-/-mice

作　　者：秦月琴 刘正霞[1] 鲁翔[2] QIN Yue-qin;LIU Zheng-xia;LU Xiang(Key Laboratory for Aging&Disease,Experimental Center,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China;Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学第二附属医院实验中心,衰老与相关疾病研究重点实验室,江苏省南京市210011 [2]南京医科大学,江苏省南京市210029

出　　处：《实用老年医学》2020年第9期890-893,共4页Practical Geriatrics

基　　金：国家自然科学基金资助项目(81970374)。

摘　　要：目的观察IL-22对高脂饮食诱导的载脂蛋白E基因敲除(ApoE^-/-)小鼠主动脉内质网应激的影响。方法24只健康雄性ApoE^-/-小鼠(8周龄)被随机分为对照(Control)组、高脂(HF)组、HF+IL-22组,每组8只。Control组给予普通饲料,另外2组给予高脂饲料喂养12周。HF+IL-22组同时腹腔注射用PBS(含5%海藻糖)稀释的重组小鼠白细胞介素(rmIL-22)溶液0.1 mL/d,浓度200 ng/mL,其余小鼠腹腔注射等量的PBS溶液(含5%海藻糖)。实验12周后,检测各组小鼠血脂水平、主动脉内质网应激相关蛋白[葡萄糖调节蛋白(GRP)78、GRP94、C/EBP同源蛋白(CHOP)]mRNA及GRP78蛋白的表达水平。结果与Control组相比,HF组TC、HDL-C、TG和LDL-C水平显著升高(P<0.05),GRP78、GRP94和CHOP的mRNA表达量亦显著升高(P<0.05),GRP78蛋白表达量也显著升高(P<0.01);HF+IL-22组较HF组TC和LDL-C水平显著降低(P<0.05),GRP78、GRP94的mRNA表达量显著降低(P<0.001),GRP78蛋白表达量也显著降低(P<0.05),且HF+IL-22组较Control组LDL-C、TC、TG、HDL-C水平增高,GPP78、CHOPmRNA、GRP78蛋白表达增高,GRP94 mRNA水平降低(P<0.05)。结论IL-22能够改善高脂饮食诱导的ApoE^-/-小鼠主动脉内质网应激。Objective To investigate the effect of interleukin-22(IL-22)on aortic endoplasmic reticulum stress induced by high-fat diet in apolipoprotein E knockout(ApoE^-/-)mice.Methods A total of 24 healthy male ApoE^-/-mice(8 weeks)were randomly divided into the control group(Control),the high-fat group(HF),and HF+IL-22 group,with 8 in each group.The Control group mice and the other mice were fed with a chow diet or a high-fat diet for 12 weeks.The HF+IL-22 group mice were intraperitoneally injected with recombinant murine-22 solution diluted with phosphate buffer solution(PBS)(5%trehalose)0.1 mL/d at a concentration of 200 ng/mL,while the other mice were intraperitoneally injected with the same amount of PBS solution(5%trehalose).After 12 weeks of the experiment,the serum lipid levels,the mRNA expressions of aortic endoplasmic reticulum stress-related proteins[glucose-regulated protein 78(GRP78,GRP94,C/EBP-homologous protein(CHOP)],and the protein expression level of GRP78 were detected.Results Compared with the Control group,the levels of total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)in the HF group and HF+IL-22 group were significantly increased(P<0.05);The mRNA expression levels of GRP78,GRP94 and CHOP were significantly increased in the HF group(P<0.05),and the expression of GRP78 protein was also significantly increased in HF group and HF+IL-22 group(P<0.01);the expression of GRP78 and CHOP was increased and the expression of GRP94 was decreased in HF+IL-22 group than that in control group.Compared with HF group,the levels of TC and LDL-C,GRP78 protein expression were significantly decreased(P<0.05),and the mRNA expression levels of GRP78 and GRP94 were significantly decreased(P<0.001).Conclusions IL-22 can attenuate endoplasmic reticulum stress induced by high-fat diet in ApoE^-/-mouse aortic tissue.

关 键 词：白细胞介素-22 高脂血症 内质网应激 主动脉 

分 类 号：R543[医药卫生—心血管疾病]