摘要
目的探讨α7烟碱型乙酰胆碱受体(α7n AChR)基因敲除对非酒精性脂肪性肝炎(NASH)小鼠肝脏炎症的影响。方法 2014年6月—2015年5月,选取40只SPF级雄性6周龄C57BL/6J小鼠和40只SPF级雄性6周龄α7n AChR基因敲除小鼠,采用随机数字表法分为C57普通饲料组、C57高脂高糖组、基因敲除普通饲料组、基因敲除高脂高糖组,每组20只。C57普通饲料组、基因敲除普通饲料组小鼠给予普通饲料喂养,C57高脂高糖组、基因敲除高脂高糖组小鼠给予高脂饲料喂养同时饮用20%果糖饮用水,喂养24周,建立NASH小鼠模型;小鼠饲养期间定期称量体质量,并且尾静脉取血检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)水平。21周时C57高脂高糖组、基因敲除高脂高糖组小鼠给予400μg/kg烟碱腹腔注射;C57普通饲料组、基因敲除普通饲料组小鼠给予等量0.9%氯化钠溶液腹腔注射,均1次/d,共3周。24周后处死小鼠,眼球取血,酶联免疫吸附试验(ELISA)法检测血清炎性细胞因子白介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平,观察小鼠肝脏外观变化及肝脏湿重,肝脏病理切片染色观察炎症程度和脂肪变性情况。结果第12、15、18、21、24周时,C57高脂高糖组、基因敲除高脂高糖组小鼠体质量较C57普通饲料组、基因敲除普通饲料组升高(P<0.05);第12、15、18、21、24周时,基因敲除高脂高糖组小鼠体质量较C57高脂高糖组升高(P<0.05)。C57高脂高糖组、基因敲除高脂高糖组小鼠第8、16、24周时血清ALT、AST、TG、TC水平,第24周时血清IL-6、TNF-α水平、肝脏湿重较C57普通饲料组、基因敲除普通饲料组升高(P<0.05);基因敲除高脂高糖组小鼠第8、16、24周时血清ALT、AST水平,第16、24周时血清TG、TC水平,第24周时血清IL-6、TNF-α水平、肝脏湿重较C57高脂高糖组升高(P<0.05)。病理切片苏木素-伊红(HE)、油红染色结果显示:
Objective To investigate the effect of α7n AChR gene knockout on the liver inflammation of non- alcoholic steatohepatitis（ NASH） mice. Methods From June 2014 to May 2015,40 SPF male 6- week- old C57 BL /6J mice and 40 SPF male 6- week- old α7n AChR gene knockout mice were selected. The mice were divided into C57 mice normal diet group（ group 1）,C57 mice high fat and fructose diet group（ group 2）,gene knockout mice normal diet group（ group 3）,gene knockout mice high fat and fructose diet group（ group 4）,with 20 rats in each group. Group 1 and group 3 were fed up with either normal feed,group 2 and group 4 were fed up with high- fat feed plus 20% fructose drinking water,24 weeks to generate an NASH model. The body weight of the mice during the feeding period was measured on a regular basis,and blood was sampled from the caudal vein to detect the levels of ALT,AST,TG and TC. In week 21,group 2 and group 4 were given 400 μg / kg nicotine by intraperitoneal injection,and group 1 and group 3 were given the same volume of 0. 9% sodium chloride solution by intraperitoneal injection for one time per day for 3 weeks. 24 weeks later,the mice were killed. Blood was sampled from eyeball to detect the levels of IL-6 and TNF-α by ELISA method,the changes of color and liver wet weight were recorded,and liver pathological section staining was conducted to observe inflammation degree and fatty degeneration. Results In week 12,15,18,21 and 24,group 2 and group 4 were higher than group 1 and group 3 in body weight（ P〈0. 05）. In week 12,15,18,21 and 24,group 4 was higher than group 2 in body weight（ P〈0. 05）. Group 2 and group 4 had higher ALT,AST,TG and TC levels in week 8,16 and 24 and higher IL-6 and TNF-α levels and higher liver wet weight in week 24 than group 1 and group3（ P〈0. 05）; group 4 had higher ALT and AST levels in week 8,16 and 24,higher TG and TC levels in week 16 and 24,higher IL-6 and TNF-α levels and higher liver wet weight in week 24 than group 2（ P〈0. 05）. The pat
出处
《中国全科医学》
CAS
CSCD
北大核心
2016年第23期2802-2809,共8页
Chinese General Practice
基金
国家自然科学基金资助项目(81100279)
浙江省新苗人才计划项目(2015R410013)
