生物钟蛋白Rev-erbα激动剂抑制高脂饮食诱导小鼠前列腺组织炎症的实验研究  

Circadian clock protein Rev-erbα agonist inhibits high-fat diet-induced inflammation of the prostate tissue in mice

作　　者：何跃[1,2] 徐航 冯德超 曹德宏 艾建忠[2] 杨璐 魏强[2] HE Yue;XU Hang;FENG Dechao;CAO Dehong;AI Jianzhong;YANG Lu;WEI Qiang(Department of Urology,Suining Central Hospital,Suining 629000,China;Department of Urology,Institute of Urology,West China Hospital,Sichuan University,Chengdu 610041)

机构地区：[1]遂宁市中心医院泌尿外科,四川遂宁629000 [2]四川大学华西医院泌尿外科/泌尿外科研究所,成都610041

出　　处：《中国实验动物学报》2022年第4期469-475,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(81974099,81770756);成都中医药大学“杏林学者”学科人才科研提升计划医药专项(YYZX2021110)。

摘　　要：目的验证生物钟蛋白Rev-erbα激动剂是否能够抑制高脂饮食诱导的小鼠前列腺组织炎症,并探讨其机制。方法C57B/6J雄性小鼠分为4组:普通饮食组;高脂饮食组;高脂饮食+SR9009组;高脂饮食+control组。检测小鼠体重、外周血胆固醇(TC)、甘油三酯(TG)及前列腺重量。前列腺组织HE染色并转录组测序,免疫组化评估IL-6、IL-8、IL-1β、NF-κB-P65和CCL21的表达水平。结果与普通饮食组相比,高脂饮食组小鼠的体重、前列腺指数、血清TG和TC水平均明显升高,高脂饮食+SR9009组小鼠的体重、前列腺指数、血清TG和TC水平明显低于高脂饮食+control组。HE染色,高脂饮食组小鼠前列腺组织内炎性细胞浸润较普通饮食组增多,SR9009干预后的高脂饮食小鼠前列腺组织炎性细胞浸润减少。转录组测序差异基因分析NF-κB通路中的Ccl21a、Ccr7、Tlr4、Il6、Il1b、Cxcr2的表达水平在高脂饮食组较普通饮食组升高,而其表达水平在高脂饮食+SR9009组较高脂饮食+control组降低。IL-6、IL-8、IL-1β、NF-κB-P65和CCL21a在4组小鼠前列腺中的表达强度差异趋势与测序结果的差异趋势一致。结论生物钟蛋白Rev-erbα可能通过NF-κB通路调节高脂饮食诱导的前列腺组织炎症水平。Objective To verify whether Rev-erbαagonists can inhibit the inflammation of prostate tissue in mice induced by a high-fat diet,and to explore the mechanism of action.Methods C57B/6J male mice were divided into four groups:normal diet group,high-fat diet group,high-fat diet+SR9009 group,high-fat diet+control group.The body weight,peripheral blood cholesterol,triglyceride level,and prostate weight were measured.The prostate tissue was stained with hematoxylin-eosin(HE),subjected to transcriptome sequencing,and the expression levels of IL-6,IL-8,IL-1β,NF-κB-P65,and CCL21 were evaluated by immunohistochemistry.Results Compared with the normal diet group,the body weight,prostatic index,and the serum TG and TC levels of mice in the high-fat diet group were significantly increased,and the body weight,prostatic index,and serum TG and TC levels of the mice in the high-fat diet+SR9009 group were significantly lower than those of the high-fat diet+control group mice.HE staining showed that inflammatory cell infiltration into the prostate tissue of the mice in the high-fat diet group was increased compared with the normal diet group,and inflammatory cell infiltration into the prostate tissue of the mice on the high-fat diet was reduced after intervention with SR9009.The expression levels of Ccl21a,Ccr7,Tlr4,Il6,Il1b,and Cxcr2 were higher in the high-fat diet group than in the normal diet group,as demonstrated by heatmap analysis,but these expression levels were lower in the high-fat diet+SR9009 group than in the high-fat diet+control group.The differences in the expression intensity of IL-6,IL-8,IL-1β,NF-κB-P65,and CCL21a in the prostate of the four groups of mice were consistent with the differences in the sequencing result.Conclusions The circadian clock protein Rev-erbαcan regulate the inflammation level of prostate tissue induced by a high-fat diet through the NF-κB pathway.

关 键 词：组织炎症 生物钟蛋白Rev-erbα 前列腺 小鼠 

分 类 号：Q95-33[生物学—动物学]