瘦素受體OB-RGRP水平對脂肪細胞的影響及其作用機制研究

石衛紅 李小林 巫國輝

[摘要]目的：為了探討不同水平的瘦素受體（OB-RGRP）調節大鼠脂肪細胞的研究及其作用機制，明確其對脂肪細胞的影響，為瘦素受體治療肥胖癥提供理論依據。方法：原代分離大鼠脂肪細胞，利用油紅O染色進行鑒定，構建過表達OB-RGRP和干擾OB-RGRP載體，利用Western blot驗證細胞轉染效果，并檢測JAK2、STAT3及其磷酸化的表達情況。結果：細胞分離正確，構建的OB-RGRP-siRNA轉染有效，與對照組相比，過表達OB-RGRP組的p-JAK2和p-STAT3表達明顯升高，干擾OB-RGRP組的p-JAK2和p-STAT3表達明顯下降，差異具有統計學意義（P<0.05）。而JAK2、STAT3總蛋白各組之間無差異。結論：OB-RGRP水平通過JAK2/STAT3信號通路在調節瘦素抵抗中起著重要作用，調節脂肪代謝，有助于改善瘦素抵抗及肥胖防治。

[關鍵詞]OB-RGRP;瘦素受體;Western blot;JAK2/STAT3信號通路;脂肪細胞;肥胖癥

[中圖分類號]R329.2+8 ? ?[文獻標志碼]A ? ?[文章編號]1008-6455（2019）11-0090-03

Abstract： Objective ?To investigate the mechanism of leptin receptors（OB-RGRP） in regulating obesity In order to investigate the regulation of different levels of leptin receptor ?on adipocytes in rats and its mechanism of action， and to clarify its effect on adipocytes， so as to provide theoretical basis for the treatment of obesity by leptin receptor. Methods ?Primary rat adipocytes were isolated and identified by oil red O staining. OB-RGRP overexpressed and OB-RGRP interfering vectors were constructed. The cell transfection effect was verified by Western blot， and the expression of JAK2， STAT3 and their phosphorylation were detected. Results ?The cells were isolated correctly and the constructed OB-RGRP-siRNA was effective in transfection. Compared with the control group， the overexpression of p-JAK2 and p-STAT3 in the OB-RGRP group was significantly increased， while the expression of p-JAK2 and p-STAT3 in the OB-RGRP group was significantly decreased， and the difference was statistically significant （P <0.05）.There was no difference between JAK2 and STAT3 groups. Conclusion ?OB-RGRP level plays an important role in regulating leptin resistance through the JAK2/STAT3 signaling pathway， regulating fat metabolism and contributing to the improvement of leptin resistance and the prevention and treatment of obesity.

Key words： OB-RGRP; leptin receptor; Western blot; JAK2/STAT3 signal path; adipocyte; adiposis

隨著經濟的發展和人們生活水平的提高，肥胖問題越來越受到關注，發達國家肥胖率顯著高于發展中國家，而我國近年來的肥胖率也顯著升高[1-2]。據報道，我國成人肥胖率由1989年的1.32%迅速增長到2009年的9.62%[3]。肥胖是由多種因素決定的，過度飲食，超范圍的熱量攝取，運動量不足以及一些疾病或遺傳等因素均可能導致肥胖。除去外在的飲食與運動因素，肥胖還與基因的調控有關，瘦素（1eptin）是由肥胖基因（OB gene）編碼，脂肪組織分泌的激素具有抑制食欲、調節能量代謝，通過結合瘦素受體（1eptin receptor，OB-RGRP）發揮其調節脂肪蛋白質等能量代謝的作用[4-5]。因此機體的瘦素水平或是瘦素受體的水平對肥胖起到關鍵作用。

本研究通過構建瘦素受體（OB-RGRP）過表達載體和干擾載體，轉染至大鼠脂肪細胞，通過Western blot檢測相關蛋白的表達，探索不同瘦素受體水平對大鼠脂肪細胞的影響及其可能的作用機制和調節方式。……