基于JAK/STATs通路探索不同层次穴位埋线治疗单纯性肥胖的作用机制

Acupoint catgut embedding therapy, as a safe, effective and lasting treatment for Simple Obesity, can regulate the leptin level in central and peripheral region favorably, which has a wide clinical application foregroud. In clinic, which layer is better for acupoint catgut embedding therapy has not been proposed clearly, which results in the efficacy of losing weight is unknown and the low repeatability. We have come to a conclusion that the catgut embedding therapy in the adipose layer is better than the muscular layer. According to the fundamental researches, leptin passed the Janus kinase/signal transducer and activator of transcription pathway (JAK/STATs) through combining with the leptin receptors, and in which can be expressed to fulfill the purpose of losing weight. Meanwhile, the leptin can generate the Suppressor of Cytokine Signaling-3 (SOCS-3) through JAK/STATs pathway. However, SOCS-3 can inhibit the JAK/STATs pathway reactively, which leads to the leptin resistance. There are no systematic observations in how acupoint catgut embedding therapy treats the simple obesity recently, and most of researches focused on the individual indicators in the molecular domain, such as SOCS-3. Therefore, our study aims to observe the protein and gene expressions of JAK2、STAT3 and SOCS-3 in adipose tissues and hypothalamus after adopting the acupoint catgut embedding therapy to rats with simple obesity in the adipose layer and muscular layer. We intend to discuss the therapeutic effect mechanisms of how acupoint catgut embedding therapy treats simple obesity in different layers in terms of JAK/STATs. And then we hope to obtain the best layer through acupoint catgut embedding therapy for simple obesity and provide the experimental and theoretical basis for stabling and enhancing the clinical effect of simple obesity with acupoint catgut embedding therapy.

穴位埋线是一种持久安全有效治疗单纯性肥胖的治疗手段，能良性地调节肥胖机体中枢与外周的瘦素水平,具有广泛的临床应用前景。临床治疗中,埋线层次未明确提出，导致减肥疗效不确切，可重复性低。笔者前期临床研究中得出，穴位埋线埋于脂肪层减肥疗效优于肌肉层。基础研究中瘦素通过与瘦素受体结合后主要经过Janus激酶/信号转导及转录激活子通路，使之得以表达，达到减肥目的，同时瘦素又通过JAK/STATs通路产生细胞因子信号转导抑制因子-3，而SOCS-3反馈性地抑制JAK/STATs通路，产生瘦素抵抗。目前在穴位埋线治疗单纯性肥胖中缺乏对JAK/STATs通路的系统观察，仅局限在分子领域中对单个指标的监测，如：SOCS-3。故本课题拟观察肌肉层、脂肪层穴位埋线对单纯性肥胖大鼠JAK2、STAT3及SOCS-3的蛋白与基因在脂肪组织及下丘脑中的表达，从JAK/STATs通路探讨不同层次穴位埋线治疗单纯性肥胖。

目的 观察不同层次穴位埋线对单纯性肥胖大鼠体重、瘦素及JAK2/STAT3通路相关mRNA及蛋白表达的影响。.方法：1月龄SD雄性大鼠60只，随机分为正常组10只、造模组50只。正常组予普通饲料喂养，造模组予高脂饲料喂养。将造模成功的大鼠随机分为模型组、脂肪层埋线组、脂肪层埋线+AG490组、肌肉层埋线组、肌肉层埋线+AG490组各10只。比较各组大鼠治疗前后体重、血清瘦素及JAK2/STAT3通路相关mRNA及蛋白表达的差异。.结果：治疗后，体重方面：脂肪层埋线组和肌肉层埋线组体重均明显降低（P<0.01），但脂肪层埋线组明显低于肌肉层埋线组（P<0.01）。瘦素表达方面：脂肪层埋线组、肌肉层埋线组明显降低（P<0.05），脂肪层埋线组瘦素水平均显著低于肌肉层模型组（P<0.05）。JAK2/STAT3通路相关mRNA表达：脂肪层埋线组、肌肉层埋线组的JAK2、STAT3、LepR的mRNA表达量显著增加（P<0.05），SOCS3的mRNA表达量显著下降（P<0.05）。而脂肪层埋线+AG490组、肌肉层埋线+AG490组中仅JAK2、LepR的mRNA表达量增加（P<0.05），脂肪层埋线组的LepR、JAK2、STAT3的表达量明显高于肌肉层埋线组（P<0.05），而SOCS3的表达量明显低于肌肉层埋线组（P<0.05）。JAK2/STAT3通路相关蛋白表达：脂肪层埋线组、肌肉层埋线组JAK2、STAT3、LepR蛋白表达量显著增加（P<0.05），SOCS3蛋白表达量显著下降（P<0.05）。而脂肪层埋线+AG490组、肌肉层埋线+AG490组中仅SOCS3的蛋白表达量显著降低（P<0.05）。脂肪层埋线组的LepR、JAK2、STAT3的表达量明显高于肌肉层埋线组（P<0.05），而SOCS3的表达量明显低于肌肉层埋线组（P<0.05）。.结论：穴位埋线能有效减轻肥胖大鼠体重，脂肪层穴位埋线在减轻体重方面疗效较好可能是因为改善瘦素抵抗以及调控JAK2/STAT3通路相关mRNA及蛋白表达有关。