补脾胃泻阴火升阳汤干预糖尿病大血管并发症实验研究

The experimental intervention of diabetic macrovascular complications with Bupiwei Xieyinhuo Shengyang Decoction

关键词:  阴火  肠道菌群  糖尿病大血管并发症  补脾胃泻阴火升阳汤  甘温除热

Key words:  yin fire  intestinal flora  diabetic macrovascular complications  Bupiwei Xieyinhuo Shengyang Decoction  relieving heat with sweet and warm traditional Chinese medicine therapy

摘要:

[目的] 通过观察补脾胃泻阴火升阳汤对糖尿病大血管并发症豚鼠模型的肠道菌群以及动脉损伤的影响,探讨甘温除热法干预糖尿病血管并发症的可能机制。[方法] 雄性Hartley豚鼠随机分为空白组、模型组、干预组。对模型组与干预组行腹腔注射链尿佐菌素(STZ)联合高脂餐诱导糖尿病大血管并发症模型;干预组予补脾胃泻阴火升阳汤。观察各组血清氧化三甲胺(TMAO)、肿瘤坏死因子-α(TNF-α)、脂多糖(LPS)、细胞间黏附分子(ICAM)-1、血管细胞黏附分子(VCAM)-1水平和主动脉结构,以及粪便菌群丰度、菌群结构。[结果] 与空白组、干预组比较,模型组TMAO水平显著升高(P<0.01);空白组与干预组间TMAO水平无统计学差异(P>0.05)。与空白组比较,模型组LPS、VCAM-1水平显著升高(P<0.05);但空白组与干预组间、模型组与干预组间未见统计学差异(P>0.05)。与空白组比较,模型组的瘤胃球菌属(P<0.01)、节杆菌属、土壤红杆菌属、Ileibacterium、理研菌属、粪杆菌属丰度显著降低(P<0.05);UCG-005(P<0.01)、甲烷短杆菌属、achnospiraceae_NK4A136_group、Colidextribacter、Akkermansia丰度显著增高(P<0.05)。与模型组比较,干预组的节杆菌属、土壤红杆菌属(P<0.01)、乳酸菌、Colidextribacter、Papillibacter、Christensenellaceae(克里斯滕森菌科)_R-7_group、脱硫弧菌丰度显著降低(P<0.05);粪杆菌属丰度显著增高(P<0.01)。主动脉弓HE染色切片可见模型组出现较多空泡样变性,干预组空泡样变性较模型组明显减少。[结论] 脾胃虚弱是阴火形成的病理基础,阴火灼伤是糖尿病大血管并发症形成和发展的重要病机。以补脾胃泻阴火升阳汤为代表的甘温除热法在干预糖尿病大血管并发症方面具有一定作用,其机制可能是通过调节异常的肠道菌群。

Abstract:

[Objective] To investigate the possible mechanism of the intervention of relieving heat with sweet and warm traditional Chinese medicine therapy in diabetic macrovascular complications by observing the effects of Bupiwei Xieyinhuo Shengyang Decoction on intestinal microflora and arterial damage in guinea pigs with diabetic macrovascular complications.[Methods] Male Hartley guinea pigs were divided into blank group,model group and intervention group randomly.Model group and intervention group were given intraperitoneal injection of STZ combined with high fat diet to induce diabetic macrovascular complications.Intervention group were given Bupiwei Xieyinhuo Shengyang Decoction.The levels of serum TMAO,TNF-α,LPS,ICAM-1,VCAM-1,aorta structure,fecal flora abundance and flora structure were observed.[Results] Compared with blank group and intervention group,TMAO level in model group was significantly increased (P<0.01).There was no significant difference in TMAO levels between the blank group and the intervention group (P>0.05).Compared with blank group,LPS and VCAM-1 levels in model group were significantly increased (P<0.05).However,there were no significant difference between the blank group and the intervention group or between the model group and the intervention group (P>0.05).Compared with blank group,The abundance of Ruminococcus (P<0.01),Arthrobacter,Solirubrobacter,Ileibacterium,Alistipes and Faecalibacterium in model group was significantly reduced (P<0.01).While the abundance of UCG-005(P<0.01),Methanobrevibacter,achnospiraceae_NK4A136_group,Colidextribacter and Akkermansia in model group was significantly increased (P <0.05).Compared with model group,the abundance of Arthrobacter,Solirubrobacter (P <0.01),Lactobacillus,Colidextribacter,Papillibacter,Christensenellaceae_R-7_group and Desulfovibrio in the intervention group was significantly reduced (P <0.05),and Faecalibacterium was significantly increased (P<0.01).HE staining section of aortic arch showed more vacuolar degeneration in the model group,and comparatively less vacuolar degeneration in the intervention group.[Conclusion] Weakness of spleen and stomach is the pathological basis of the formation of yin fire,and injury made by yin fire is an important pathogenesis of the formation and development of diabetic macrovascular complications.The relieving heat with sweet and warm traditional Chinese medicine therapy which is represented by Bupiwei Xieyinhuo Shengyang Decoction,plays a certain role in the intervention of diabetic macrovascular complications,which may be achieved through the regulation of intestinal flora structure.