Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, China.
Hospital of Chengdu University of Traditional Chinese Medicine, TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Sichuan, Chengdu, China.
J Cardiovasc Pharmacol. 2023 Apr 1;81(4):300-316. doi: 10.1097/FJC.0000000000001403.
Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.
血管内皮细胞构成了动脉血管的内壁，易受到高血糖引起的氧化应激和细胞凋亡的损伤。有报道称，非编码 RNA 参与调控氧化应激和细胞凋亡。参芪复方（SQC）作为一种传统的草药制剂，在中国成功治疗糖尿病血管疾病已有 20 多年的历史。虽然 SQC 能保护血管内皮细胞已得到广泛证实，但其中的分子机制尚不清楚。本研究选用自发性 2 型糖尿病大鼠（Goto-Kakizaki 大鼠）作为模型动物，该大鼠持续摄入高脂肪饮食。实验共分为 6 组（对照组、模型组、二甲双胍组和 SQC 低、中、高剂量组），每组 15 只。灌胃给药，各组给予相同体积（5.0 mL/kg/d），每天 1 次，连续 12 周。处死大鼠后取其胸主动脉。检测胸主动脉氧化还原状态、胸主动脉组织病理学观察、胸主动脉内皮细胞凋亡、全转录组测序、生物信息学分析和 qRT-PCR。结果显示，SQC 可预防高糖诱导的氧化应激和细胞凋亡。在高糖环境下，SQC 可明显逆转 1 个下调的新型环状 RNA（circRNA.3121）、3 个下调的长链非编码 RNA（Skil.cSep08、Shawso.aSep08-unspliced 和 MSTRG.164.2）和 1 个上调的 mRNA（Pcdh17）的表达。SQC 主要通过调节 ncRNA 抑制细胞凋亡和氧化应激来保护血管内皮细胞。
