Zhao Tingting, Xiang Qian, Lie Beifeng, Chen Deqi, Li Minyi, Zhang Xi, Yang Junzheng, He Bao, Zhang Wei, Dong Ruixue, Liu Yadi, Gu Junling, Zhu Quan, Yao Yijing, Duan Tingting, Li Zhenghai, Xu Youhua
Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao, PR China.
Institute of Consun Co. for Chinese Medicine in Kidney Diseases, Guangdong Consun Pharmaceutical Group, Dongpeng Road 71, Guangzhou, PR China.
Heliyon. 2023 Mar 2;9(3):e14171. doi: 10.1016/j.heliyon.2023.e14171. eCollection 2023 Mar.
Diabetic nephropathy (DN) is the primary cause of end-stage renal disease worldwide. Although etiology for DN is complex and still needs to be fully understood, lipid metabolism disorder is found to play a role in it. Previously, we found Yishen Huashi (YSHS) granule could inhibit diabetic damage and reduce level of microalbuminuria (mALB) in DN animals. To explore its role and mechanism in lipid metabolism under DN settings, this study was designed.
DN rats were induced by streptozotocin (STZ), HepG and CaCO cells were applied for study. Hematoxylin-Eosin (HE), periodic acid-Schiff (PAS) staining, and Transmission Electron Microscopy (TEM) were applied for histological observation; 16s Sequencing was used for intestinal microbiota composition analysis; western blotting (WB) and immunofluorescence were carried out for molecular biological study, and enzyme-linked immunosorbent assay (ELISA) was used for lipid determination.
YSHS administration significantly reduced levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL-C), while increased level of high-density lipoprotein (HDL-C); meanwhile, histological changes and steatosis of the liver was ameliorated, integrity of the intestinal barrier was enhanced, and dysbacteriosis within intestinal lumen was ameliorated. Mechanism study found that YSHS modulated mitophagy within hepatocytes and inhibited mTOR/AMPK/PI3K/AKT signaling pathway.
In conclusion, we found in the present study that YSHS administration could ameliorate lipid metabolism disorder in DN animals, and its modulation on intestinal-liver axis played a significant role in it.
糖尿病肾病（DN）是全球终末期肾病的主要病因。尽管DN的病因复杂且仍需充分了解，但发现脂质代谢紊乱在其中起作用。此前，我们发现益肾化湿（YSHS）颗粒可抑制糖尿病损伤并降低DN动物的微量白蛋白尿（mALB）水平。为探讨其在DN背景下脂质代谢中的作用及机制，设计了本研究。
用链脲佐菌素（STZ）诱导DN大鼠，应用HepG和CaCO细胞进行研究。采用苏木精-伊红（HE）、过碘酸-希夫（PAS）染色及透射电子显微镜（TEM）进行组织学观察；采用16s测序分析肠道微生物群组成；进行蛋白质免疫印迹（WB）和免疫荧光进行分子生物学研究，采用酶联免疫吸附测定（ELISA）测定脂质。
给予YSHS可显著降低总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白（LDL-C）水平，同时提高高密度脂蛋白（HDL-C）水平；同时，肝脏的组织学变化和脂肪变性得到改善，肠屏障完整性增强，肠腔内的菌群失调得到改善。机制研究发现，YSHS调节肝细胞内的线粒体自噬并抑制mTOR/AMPK/PI3K/AKT信号通路。
总之，我们在本研究中发现，给予YSHS可改善DN动物的脂质代谢紊乱，其对肠-肝轴的调节在其中起重要作用。
