The Effects Of Didang Decoction On The Retina Of STZ-induced Diabetic Rats

Background:Diabetic retinopathy (DR) is one of the most serious and common complications of diabetes. Diabetes can cause the abnormality of capillary vessel of the tissues and organs in the body. With respect to eyes, it leads to ischemia, hypoxia, angiogenesis, fibrous proliferation, retinal detachment, and even loss of vision.The pathogenesis of DR is very complex, and has not yet been fully elucidated. In traditional Chinese medicine, different titles have been given to describe visual disturbance caused by diabetic retinopathy, based on different degrees of the lesion, such as " sudden loss of vision ", "diabetes eye disease"," blurring of vision" and so on. As the disease has the characteristics of the normal external eye and sheltering from inside, it is attributed to the "cataract" eye disease in traditional Chinese medicine. The Didang decoction originating from Zhang Zhongjing's " Treatise on Cold-Induced and Miscellaneous Diseases " in the Eastern Han dynasty, composed of the rhubarb, peach kernel, gadfly and leeches, is a classic treatment regimen for excess syndrome of blood accumulation, with the effect of activate blood, activate collaterals and expel stasis. In this study, we aim to study the Didang decoction through morphology and gene expression pathways, and analyse the possible mechanisms of Didang decoction affecting on diabetic retinopathy in rats, in order to find new ideas for prevention and treatment of DR using Chinese medicine.Objective:Through inducing the formation of STZ diabetic retinopathy rat model, we explored the influence of Didang decoction on serum markers, morphology and gene expression in rats with diabetic retinopathy.Methods:After being injected streptozotocin (STZ) into the caudal vein and fed with the high fat diet, diabetes model rats were divided into normal control group, model control group, Didang decoction late group, Didang decoction interim group, Didang decoction early group, atorvastatin calcium group and the rosiglitazone group. We observed the growth status, body weight, blood glucose and blood insulin, morphological changes of retina, the immunohistochemical and pathological changes of ICAM-1 and VCAM-1, gene expression of VEGF, TGF-?1 and PKC-?2 in retina by RT-PCR, and explored the possible mechanism of Didang decoction's influence on diabetic retinopathy.Results:STZ-induced diabetic rat model was established successfully. In end of the experiment (24 weeks from the start point), compared with normal control group, the body weight of the rats in other groups was significantly higher, indicating that high fat diet helped to increase the body weight of the rats and contributed to establish the diabetic rat model; compared with other diabetic model group, the body weight of model control group decreased showed no significant; compared with the model control group, the body weight of the rats in rosiglitazone group increased, and the body weight of the rats in the Didang decoction intervention groups and simvastatin groups did not change significantly, indicating that the effect of lowing glycemic level of rosiglitazone could counterwork against the role of body weight reduction of diabetes, and Didang decoction and simvastatin had no effect on the body weight of diabetic rats. Compared with the normal control group, the blood glucose of the rats of STZ induced diabetes model was significantly increased; compared with the model control group, the blood glucose of the rats in rosiglitazone group was reduced, and the blood glucose of the rats in Didang decoction intervention groups and simvastatin group did not change significantly; compared with the normal control group, the retinas stained by HE of the rats in model control group had irregular and oedematous structure, disordered cells, and some cells prominent from the inner limiting membrane observed under light microscope; compared with the normal control group, the ICAM-1 and VCAM-1 expressed in the retinas of the rats in model control group after stained through imrnunohistochemical method increased, indicating that these retinal tissue of diabetic rats pathologically changed; compared with the model control group, Didang decoction interim group, Didang decoction early group, Simvastatin group and rosiglitazone group pathologically changed lighter; RT-PCR assay showed that the VEGF, TGF-?1 and PKC-?2 mRNA expressed in the retinal tissue in the normal control group were light; and compared to the normal control group, the expression of VEGF, TGF-?1 and PKC-?2 mRNA in the retinal tissue in model control group were elevated to some extent; the expression of VEGF, TGF-?1 and PKC-?2 mRNA in retinal tissue in Didang decoction interim group and Didang decoction early group were reduced to some extent.Conclusion:In this study, we observed the retinopathy in diabetic rats based on STZ-induced diabetic rat model, and found that the early and interim intervention with Didang decoction in the rats could affect the occurrence and development of diabetic retinopathy. After the early and interim intervention with Didang decoction, the retinas of the diabetic rats are significant protected and the procedure of the pathogenesis of diabetic retinas slowed down; and diabetic retinopathy is relatively minor compared with the model control group; this may be associated with the role of Didang decoction through reducing the expression of ICAM-1 and VCAM-1 in the retinal tissue, decreasing the expression of VEGF, TGF-?1 and PKC-P2 mRNA, and inhibiting the inflammatory response, and so on.