ABSTRACT
Object: To investigate the protective effect of Qizhi hypoglycemic tablets on eye diseases in strepto- zotocin-induced diabetic rats and explore its possible mechanism. Methods: Streptozotocin was used to prepare diabetic model in rats. The diabetic model rats were given Qizhi hypoglycemic tablets(780 mg/kg),metformin hydrochloride tab- lets(200 mg/kg)or glibenclamide tablets(1.5 mg/kg)via intragastric administration once a day for three months,and the dynamic changes in eye diseases were investigated. The examined index included blood glucose level,lens opacity, serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT),retina expression of collagen, matrix metalloproteinase-2(MMP-2)and tissue inhibitor of matrix metalloproteinase-1(TIMP-1). Network pharmacology was used to analyze protective mechanism. Results: Compared with the normal group,the model rats showed significant hyperglycemia(P0.05). Compared with the model group,Qizhi hypogly- cemic tablets also had hypoglycemic effect(P<0.05),which could improve hyperglycemia,polyuria and emaciation (P<0.01),significantly reduce the degree of retinal turbidity(P<0.01)and up-regulate the expression of retinal Colla- genand TIMP-1(P<0.01). According to the network pharmacology analysis,Qizhi hypoglycemic tablets could regu- late the cell proliferation and apoptosis via VEGF and MAPK signals. Conclusion: Qizhi hypoglycemic tablets could im- prove the ophthalmic disease in diabetic rats,which might be a promising medicine for the treatment of diabetic ophthal- mic disease.
ABSTRACT
This study aimed to determine the protective effect of Qizhi hypoglycemic tablet (QZHGT) on foot ulcer in diabetic rats and explore its possible mechanism. Diabetes was induced by streptozotocin injection in rats. The rats received QZHGT (780 mg·kg-1), metformin hydrochloride tablet (Metf, 200 mg·kg-1) or glibenclamide tablet (Glib, 1.5 mg·kg-1) alone via intragastric administration once a day for three months. Food ulcer was prepared by foot skin excision after drug therapy lasted for two months, and the dynamic changes in food ulcer healingwere determined. During the experiment, blood glucose, serum levels of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS), factor Ⅲ (FⅢ) and four coagulation parameters [thrombin time (TT), activated partial thromboplatin time (APTT), prothrombin time (PT), fibrinogen (FIB)] were detected. Finally, the protective mechanisms of QZHGT against diabetes and foot ulcer were analyzed by network pharmacology, and immunohistochemistry was used to confirm the expression of transforming growth factor-β (TGF-β) and nuclear factor κB (NF-κB) in pancreatic tissue. All animal procedures were approved by the Animal Experimentation Ethics Committee of Henan University (permission number HUSAM 2016-288). The results showed that the lasting hyperglycemia, polydipsia, polyphagia, polyuria and body weight lost took place in model rats compared to those in normal rats. These model rats also showed an increase in serum VEGF and iNOS, FⅢ, TT, APTT and PT, and a reduction in FIB and wound healing. Metf or Glib significantly improved hyperglycemia, polydipsia, polyphagia, polyuria and emaciation, but failed to ameliorate hypercoagulation and wound healing. QZHGT showed a similar effect on polydipsia, polyphagia, polyuria and emaciation to Metf or Glib, although it was inferior to them in hypoglycemic action. Importantly, QZHGT significantly improved hypercoagulation and wound healing, and attenuated serum VEGF and iNOS. Network pharmacology revealed that QZHGT decreased hyperglycemia through "insulin resistance pathway", improved coagulation status through "HIF-1 signaling pathway", prevented diabetic foot ulcers through "VEGF signaling pathway", "MAPK signaling pathway" and "NF-κB signaling pathway". Immunohistochemistry showed that QZHGT could inhibit the expression of TGF-β and NF-κB in pancreatic tissue to maintain islet function in diabetic rats. In summary, these data suggest that QZHGT can prevent pancreatic injury for adjunctive hypoglycemia and diabetic foot ulcer treatment, and is a better preventive and therapeutic drug for diabetic foot ulcer.