Abstract:
OBJECTIVE To study the effects of Tibetan medicine Jikan Mingmu formula on intestinal flora, oxidative stress and vascular abnormalities in rats with diabetic retinopathy, and to explore the possible mechanism of Jikan Mingmu formula in treating diabetic retinopathy.
METHODS Model rats with diabetic retinopathy induced by high-fat diet and intraperitoneal injection of 50 mg·kg
-1 streptozotocin(STZ) were randomly divided into model control group, calcium dobesilate group, and low, medium and high dose of Jikan Mingmu formula groups, and a blank control group was set. The regular monitoring of body weight and fasting blood glucose level was carried. Continuous administration was given for 8 weeks after successful modeling for 3 months, and the level of serum superoxide dismutase(SOD), intercellular adhesion molecule-1(ICAM-1), angiotensin Ⅱ(ANG-Ⅱ) was tested. Routine pathological changes of retina was observed by hematoxylin and eosin staining, microvascular changes was observed by digested patch, the protein expression of vascular endothelial growth factor(VEGF) and hypoxia-inducible factor-1α(HIF-1α) in retinal tissue was observed by immunofluorescence. The effects of Tibetan medicine Jikan Mingmu formula on the structure of rats' intestinal flora was analyzed by 16S rDNA high-throughput sequencing technology.
RESULTS Jikan Mingmu formula could slow down the body weight decline of model rats, but it had no significant effect on blood glucose. And it could reduce pathological changes of retina and improve the morphology of retinal vascular disorders. Jikan Mingmu formula medium-dose group could significantly reduce the content of ICAM-1(
P<0.05). Jikan Mingmu formula could reduce the content of ANG Ⅱ, VEGF and HIF-1α significantly(
P<0.05 or
P<0.01). Jikan Mingmu formula could effectively inhibit the trend of intestinal flora diversity in the model rats, and the inhibitory effect of Jikan Mingmu formula low-dose group was the most significant. Compared with the blank control group, the intestinal flora of the model control group had significant changes at the genus level. After administration, the intestinal flora of diabetic rats began to return to normal. Among them, Jikan Mingmu formula medium-dose group had the best regulation effect on rats' intestinal flora. Principal component analysis showed that there was a significant difference between the blank control group and the model control group. The drug-administered group had significant reversal effects on the overall performance of the model rats. The best effect was achieved in the medium and the high dose group of Jikan Mingmu formula.
CONCLUSION Jikan Mingmu formula can reduce the degree of diabetic retinopathy. The protective mechanism of the retina in diabetic rats may be related to the inhibition of neovascularization and regulation of intestinal flora.