胆碱-蛋氨酸缺乏饲料诱导的非酒精性脂肪肝大鼠chemerin及其受体的表达

The expression of chemerin and chemerin receptor in rats with methionine-and choline-deficient diet induced nonalcoholic fatty liver disease

目的 探讨胆碱.蛋氨酸缺乏饲料（MCD）诱导非酒精性脂肪性肝病（nonalcoholic fatty liver disease,NAFLD）不同时期大鼠肝脏chemerin及其受体（chemokine-like receptor 1,CMKLRI）表达的动态变化.方法 Wistar大鼠随机分为对照组和MCD组.适应性喂养1周后,分别给予普通饲料和MCD饲料喂养,分别在喂养1、4、10周时处死.检测血清谷丙转氨酶（alanine transarninase,ALT）、血脂、肝功能及肝脏TG含量,并做HE染色观察肝脏形态变化;采用实时荧光定量PCR检测细胞因子chemerin及CMKLR1 mRNA水平的表达变化,并用Northern印迹进一步确认chemerin mRNA水平的表达变化.Western印迹检测小鼠血清chemerin水平.结果 MCD饲料喂养1、4和10周后,MCD组肝脏chemerin的mRNA表达逐渐下降（1.00±0.08对0.72±0.10;1.00±0.24对0.63±0.31;1.00±0.05对0.50±0.13）;CMKLR1表达逐渐上升（1.00±0.14对0.84±0.26;1.00±0.38对1.51±0.33;1.01±0.13对1.84±0.39）.血清chemerin含量减少（1.00±0.11对0.96±0.39;1.00±0.12对0.21±0.77;1.00±0.42对0.21±0.11）.结论 Chemerin及其受体的表达变化可能参与了MCD饲料诱导的非酒精性脂肪肝的发病过程.

Objective To explore the expression of chemerin and chemerin receptor （ chemokine-like receptor 1, CMKLR1） during different periods of non-alcoholic fatty liver disease （ NAFLD） rat model induced by methionine- and choline-deficient （ MCD） diet. Methods Thirty-six Wistar rats were divided into control group and MCD group in random. After one week quarantine and acclimation period, these two groups were fed either normal chow or MCD diet. The animals were respectively sacrificed at the first week, the forth week, and the tenth week. The levels of alanine transaminase （ALT）, blood lipid profile, liver function, and the content of triglyceride in liver were detected. HE staining was done to observe the morphologic change of liver. The mRNA expression changes of chemerin and CMKLR1 in liver were measured using real-time PCR, and the change in chemerin mRNA level was further confirmed in liver by Northern blot. Finally, the concentration of chemerin in serum was measured by Western blot. Results The mRNA level of chemerin decreased significantly after four and ten weeks MCD feeding, although no obvious changes were found at first week, similar changes were found in serum chemerin （1.00±0.11 vs 0.96±0.39; 1.00±0.12 vs 0.21 ±0.77; 1.00±0.42 vs 0.21 ±0. 11）. Contrasting with the change of chemerin（1.00±0.08 vs 0.72±0.10;1.00±0.24 vs 0.63±0. 31 ;1.00±0.05 vs 0.50±0.13）, the mRNA level of CMKLR1 increased after MCD feeding（ 1.00±0. 14 vs 0. 84±0. 26; 1.00±0. 38 vs 1. 51 ±0. 33; 1. 01 ±0. 13 vs 1. 84 ± 0. 39 ）. Conclusion The change of chemerin and its receptor may participate in the process of the nonalcoholic fatty liver disease.