黄连温胆汤通过lncRNA GAS5/DHX9/BECN1介导的线粒体自噬调控脂肪细胞焦亡的机制研究

肥胖是世界范围内公共健康难题，其相关慢性炎症是多种代谢性疾病的危险因素。课题组前期发现，黄连温胆汤可减轻腹型肥胖代谢综合征大鼠脂肪组织炎症细胞浸润，抑制炎性细胞因子分泌，但上游调控机制尚未明确。近期研究发现脂肪细胞焦亡可能与肥胖慢性炎症相关，而线粒体自噬参与调控细胞焦亡，因此以线粒体自噬调控脂肪细胞焦亡为侧重点挖掘黄连温胆汤的干预机制具有创新性。lncRNA是多种病理生理过程的重要调控基因，其中GAS5的过表达能够抑制脂肪生成，我们通过生信预测发现GAS5与RNA结合蛋白DHX9之间存在潜在靶向关系，而BECN1是DHX9的潜在靶点，且BECN1参与线粒体自噬的调控，因此得到科学假说：黄连温胆汤可能通过GAS5/DHX9/BECN1信号轴介导的线粒体自噬调控脂肪细胞焦亡，从而改善肥胖相关炎症状态。揭示黄连温胆汤调控脂肪细胞焦亡的可能机制，对肥胖相关慢性炎症的防治具有重要研究意义与价值。

Obesity is a public health problem worldwide, and its associated chronic inflammation is a risk factor for many metabolic diseases. The research team found early that Huanglian Wendan Decoction can reduce the infiltration of inflammatory cells in adipose tissue and inhibit the secretion of inflammatory cytokines in rats with abdominal obesity metabolic syndrome, but the upstream regulatory mechanism is not yet clear. Recent studies have found that fat cell pyrolysis may be related to obesity and chronic inflammation, and mitochondrial autophagy is involved in regulating cell pyrolysis. Therefore, focusing on mitochondrial autophagy to regulate fat cell pyrolysis is the key to exploring the intervention mechanism of Huanglian Wendan Decoction. lncRNA is an important regulatory gene for a variety of pathophysiological processes, and overexpression of GAS5 can inhibit fat production. We predicted that there is a potential targeting relationship between GAS5 and the RNA-binding protein DHX9, and BECN1 is a potential target of DHX9. In addition, BECN1 is involved in the regulation of mitochondrial autophagy, so it is scientifically hypothesized that Huanglian Wendan Decoction may regulate fat cell pyrolysis through mitochondrial autophagy mediated by GAS5 / DHX9 / BECN1 signal axis, thereby improving obesity-related inflammation. Revealing the possible mechanism of Huanglian Wendan Decoction regulating fat cell pyrolysis has important research significance and value for the prevention and treatment of obesity-related chronic inflammation.