Objective

2

To explore the possible mechanism of

Yitangkang

（益糖康） in the treatment of type 2 diabetes mellitus （T2DM）.

Methods

2

The model of T2DM was established by high-fat diet and one-time intraperitoneal injection of streptozotocin （STZ， 45 mg/kg）. The successfully-modeled 32 SD rats were randomly divided into model group，

Yitangkang

group， metformin group and probiotics group， with eight rats in each group， while 8 SD rats with ordinary diet were also set as blank group. The

Yitangkang

group was given 56 g/（kg·d） of crude

Yitangkang

by gavage； the metformin group was given 150 mg/（kg·d） of metformin hydrochloride tablets by gavage； the probiotics group was administered with 150 mg/（kg·d） of probiotics granules by gavage， while the blank group and model group were given 0.1 ml/10 g normal saline by gavage， once daily in all groups. After 4 weeks， the pathological morphology of the intestinal tissues were observed through HE staining， and the levels of blood glucose， insulin （INS）， glycosylated hemoglobin （HbAlc）， total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were measured； 16S rRNA technology was used to determine the intestinal flora structure of the intestinal content， and α diversity index analysis， species composition analysis， the linear discriminant analysis effect size （LEfSe） of species differences， and the COG function annotation were performed； the correlations between the differential intestinal flora and blood sugar and blood lipids were analyzed.

Results

2

Pathological results showed that a large number of epithelial cells were shed from the apical intestinal villi in the model group and the probiotics group； inflammatory cell focal infiltration was occasionally seen in the metformin group； the shed epithelial cells of the apical intestinal villi of the

Yitangkang

group were significantly reduced compared to those of the model group. Compared to those of the blank group， the levels of blood glucose， INS， HbAlc， TC， TG and LDL-C and the coverage index of the model group significantly increased， and the HDL-C level， the shannon index and chao index were all significantly reduced； the abundance of Actinomycota and Proteobacteria significantly increased， while the abundance of Bacteroides significantly decreased （

P

＜0.05 or

P

＜0.01）. Compared to those of the model group， the levels of blood glucose， INS， HbAlc， TG and LDL-C in the metformin group and

Yitangkang

group were significantly reduced， and the HDL-C level and the shannon index significantly increased； the blood sugar and coverage index of the probiotics group decreased； the Proteobacteria abundance of the metformin group was significantly reduced， and the Verrucomicrobia abundance significantly increased； the Bacteroides and Verrucomicrobia of the

Yitangkang

group significantly increased， and the Proteobacteria significantly decreased； the Bacteroides and Verrucomicrobia of the probiotics group significantly increased， while the Actinomycota and other bacteria were significantly reduced （

P

＜0.05 or

P

＜0.01）. There were no significant differences between the metformin group and

Yitangkang

group in all indicators （

P

＞0.05）. Compared to those of

Yitangkang

group， the levels of blood glucose， INS， HbAlc， TG and LDL-C of the probiotics group significantly increased， while the HDL-C level and the shannon index significantly decreased； the abundance of Bacteroides and Proteobacteria significantly increased， while the abundance of Actinomycota and other bacteria were significantly reduced （

P

＜0.05 or

P

＜0.01）. There were 53 differential flora （genus） in the blank group， 8 differential flora （genus） in model group， 13 differential flora （genus） in metformin group， 11 differential flora （genus） in

Yitangkang

group and 5 differential flora （genus） in probiotics group. COG functional classification showed that differential flora significantly affected carbohydrate transport and metabolism， amino acid transport and metabolism， transcription， replication， recombination and repair， ribosomal structure and biogenesis pathways. Proteobacteria was significantly positively correlated with INS and TC levels （

P

＜0.05 or

P

＜0.01）.

Conclusion

2

Yitangkang

could regulate glucose and lipid metabolism of T2DM rats， whose effect is equal to metformin and better than probiotics. The mechanism may be related to its function of improving the composition and structure of intestinal flora.