健脾升清化浊方（JSH）是基于传统中医理论和经典方剂（补中益气汤和愈夜汤）改良而成的处方。研究发现，JSH对于早期异常葡萄糖和脂质代谢的肥胖患者具有良好的效果。因此，本实验旨在研究其临床疗效和药理作用，以观察JSH的临床疗效并探讨其改善肥胖大鼠葡萄糖和脂质代谢的机制。 1.选择10名存在葡萄糖和脂质代谢异常的超重/肥胖患者，观察这些患者在接受JSH治疗前后的血清葡萄糖、血清脂质和肝损伤指标。2.动物实验：将50只SD大鼠随机分为对照组、模型组、二甲双胍组（每天120mg/kg）、JSH-低剂量组（每天5g/kg）和JSH-高剂量组（每天20g/kg），每组10只。使用60%高脂饮食饲养8周建立肥胖的Sprague-Dawley（SD）大鼠模型，并对给药组进行预防性给药8周。实验结束时，测量体重、腹部脂肪、血浆葡萄糖、血浆脂质、血浆丙氨酸氨基转移酶（ALT）和门冬氨酸氨基转移酶（AST）的水平。用酶联免疫吸附法检测血浆中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的变化，并用试剂盒检测血浆和肝组织中丙二醛（MDA）、谷胱甘肽（GSH）和过氧化氢酶（CAT）的变化。用HE染色和油红O染色观察肝脏的病理变化和脂质沉积，并用透射电子显微镜观察肝细胞线粒体数量的变化。使用RT-qPCR和Western Blot（WB）检测肝组织中与线粒体调节相关的指标PGC-1α、NRF1、TFAM、MFN2、DRP1和与凋亡相关的指标Bcl-2、Bax、caspase 8的表达。 1.经过一个月的服药后，患者的体重、BMI、2小时口服葡萄糖耐量试验（2hOGTT）、糖化血红蛋白（HbA1c）、甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）明显下降，并且肝损伤指标AST和ALT也显著降低。2.动物实验：JSH能够显著减轻体重和腹部脂肪面积，改善肥胖大鼠的葡萄糖和脂质代谢，并且还能降低肥胖大鼠血浆IL-6、IL-1β和TNF-α的含量，改善氧化应激反应。HE染色和油红O染色显示JSH能够缓解肝损伤和脂质沉积。进一步观察肝细胞超微结构显示JSH能够改善高脂饮食引起的肝线粒体减少，并促进与PGC-1α、NRF1和TFAM相关的线粒体生物发生相关指标的表达。此外，JSH能够促进MFN2和DRP1的表达，降低Bcl-2的表达并增加Bax的表达。 1.JSH能够降低超重/肥胖患者的体重、血清葡萄糖、血清脂质和肝损伤。2.动物实验：JSH通过调节PGC-1α/NRF1/TFAM信号通路促进肝线粒体生物发生，改善肥胖大鼠的葡萄糖和脂质代谢，并通过调节线粒体依赖性凋亡指标Bcl-2/Bax降低肝损伤。 Copyright © 2023. Elsevier B.V.出版

Jianpi Shengqing Huazhuo Formula (JSH) is a modified prescription based on traditional Chinese medicine theory and classic prescriptions (Buzhong Yiqi Decoction and Yuye Decoction). It has been found that JSH has a good effect on obese patients with early abnormal glucose and lipid metabolism. Therefore, this experiment was conducted to study its clinical efficacy and pharmacological effect.To observe the clinical efficacy of JSH and explore the mechanism of the formula to improve glucose and lipid metabolism in obese rats.1.10 overweight/obese patients with abnormal glucose and lipid metabolism were selected to observe the indicators of serum glucose, serum lipids and liver damage of the patients before and after treatment with JSH. 2. Animal experiment: Fifty SD rats were randomly divided into control group, model group, Metformin group (120 mg/kg/day), JSH-L group (5 g/kg/day) and JSH-H group (20 g/kg/day), with 10 rats in each group. The obese Sprague-Dawley (SD) rat model was produced by feeding 60% high-fat diet for 8 weeks, and the drug group was given prophylactic administration for 8 weeks. At the end of the experiment, body weight, abdominal fat, plasma glucose, plasma lipids, plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. The levels of interleukin-6 (IL-6), interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in plasma were detected by Elisa, and the changes of malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) in plasma and liver tissue were detected by kits. The pathological changes and lipid deposition in liver were observed by HE staining and oil red O staining, and the changes in the number of mitochondria in liver cells were observed by transmission electron microscopy. RT-qPCR and Western Blot (WB) were used to detect the mitochondrial regulation-related indicators PGC-1α, NRF1, TFAM, MFN2, DRP1 and apoptosis-related indicators Bcl-2, Bax, caspase 8 in liver tissue.1.after one month administration, the patient's body weight, BMI, 2 h oral glucose tolerance test (2hOGTT), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) decreased significantly, and the indicators of liver damage AST and ALT also decreased significantly. 2. Animal experiments: JSH can significantly reduce body weight and abdominal fat area, improve glucose and lipid metabolism, and also reduce plasma IL-6, IL-1β and TNF-α content in obese rats, and improve oxidative stress; HE staining and oil red O staining also showed that JSH can alleviate liver damage and lipid deposition in the liver. Further observations of liver cell ultrastructure showed that JSH can ameliorate the reduction of liver mitochondria caused by a high-fat diet and promote the expression of indicators of mitochondrial biogenesis related to PGC-1α, NRF1, and TFAM. Moreover, JSH could promote the expression of MFN2 and DRP1, decrease Bcl-2 and increase Bax in the liver.1.JSH can reduce body weight, serum glucose, serum lipid, and liver injury in overweight/obese patients. 2. Animal experiment: JSH regulates PGC-1α/NRF1/TFAM signaling pathway promotes liver mitochondrial biogenesis, improves glucose and lipid metabolism in obese rats, and regulates mitochondrial dependent apoptosis indicators Bcl-2/Bax to reduce liver injury.Copyright © 2023. Published by Elsevier B.V.