AIM:To evaluate the inhibitory effects of regorafenib(BAY 73-4506),a multikinase inhibitor,on corneal neovascularization(NV).METHODS:Thirty adult male Sprague-Dawley rats weighing 250-300 g,were used.Corneal NV was in...AIM:To evaluate the inhibitory effects of regorafenib(BAY 73-4506),a multikinase inhibitor,on corneal neovascularization(NV).METHODS:Thirty adult male Sprague-Dawley rats weighing 250-300 g,were used.Corneal NV was induced by NaOH in the left eyes of each rat.Following the establishment of alkali burn,the animals were randomized into five groups according to topical treatment.Group 1(n=6)received 0.9%NaCl,Group 2(n=6)received dimethyl sulfoxide,Group 3(n=6)received regorafenib 1 mg/mL,Group 4(n=6)received bevacizumab 5 mg/mL and Group 5(n=6)received 0.1%dexamethasone phosphate.On the 7d,the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea’s total area using computer-imaging analysis.The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.RESULTS:A statistically significant difference in the percent area of corneal NV was found among the groups(P【0.001).Although the Group 5 had the smallest percent area of corneal NV,there was no difference among Groups 3,4 and 5(P】0.005).There was a statistically significant difference among the groups in apoptotic cell density(P=0.002).The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups(P【0.05).The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3,4 and 5 thanin Groups 1 and 2.CONCLUSION:Topical administration of regorafenib 1mg/mL is partly effective for preventing alkali-induced corneal NV in rats.展开更多
Background Currently, there are still divergent opinions about the mechanisms of the impaired neovascularization in diabetic subjects. Due to the remarkable therapeutic effect of angiotensin-converting enzyme inhibiti...Background Currently, there are still divergent opinions about the mechanisms of the impaired neovascularization in diabetic subjects. Due to the remarkable therapeutic effect of angiotensin-converting enzyme inhibititors （ACEIs） on the reduction of blood pressure and the protection of target organs, the clinical application of this kind of drugs is very widespread. However, it is still not clear about the role and related molecular pathway of this kind of drugs in the limbs＇ postischemic revascularization. It is of major therapeutic importance to resolve these questions. This study aimed to investigate the reasons of the impaired angiogenesis in the hind limbs of rats with diabetic ischemia, the role and related molecular mechanisms of ACEI in postischemic revascularization. Methods Hind limbs ischemia was induced in diabetic rats by right femoral artery excision. Diabetic rats were randomly allocated to one of the following treatments for 4 weeks： ACEI by perindopril; perindopril in combination with a nitric oxide synthase （NOS） inhibitor; perindopril in combination with bradykinin （BK）-B1 receptor （BIR） antagonist or saline. The differences of angiogenesis, the mRNA and protein expression of endothelial nitric oxide synthase （eNOS）, vascular endothelial growth factor （VEGF） and basic fibroblast （bFGF）, constitutive nitric oxide synthase （cNOS） activity and nitric oxide （NO） content were observed after treatment. Results In non-ischemic hind limbs, no significant changes in capillary density, or the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity were observed among all groups. On the contrary, in ischemic hind limbs, the capillary density in diabetic rats decreased by 27% when compared with the control rats, so did the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity （P 〈0.05）. The capillary density was increased by 1.65-fold in the perindopril treatment group in reference to unt展开更多
文摘AIM:To evaluate the inhibitory effects of regorafenib(BAY 73-4506),a multikinase inhibitor,on corneal neovascularization(NV).METHODS:Thirty adult male Sprague-Dawley rats weighing 250-300 g,were used.Corneal NV was induced by NaOH in the left eyes of each rat.Following the establishment of alkali burn,the animals were randomized into five groups according to topical treatment.Group 1(n=6)received 0.9%NaCl,Group 2(n=6)received dimethyl sulfoxide,Group 3(n=6)received regorafenib 1 mg/mL,Group 4(n=6)received bevacizumab 5 mg/mL and Group 5(n=6)received 0.1%dexamethasone phosphate.On the 7d,the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea’s total area using computer-imaging analysis.The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.RESULTS:A statistically significant difference in the percent area of corneal NV was found among the groups(P【0.001).Although the Group 5 had the smallest percent area of corneal NV,there was no difference among Groups 3,4 and 5(P】0.005).There was a statistically significant difference among the groups in apoptotic cell density(P=0.002).The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups(P【0.05).The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3,4 and 5 thanin Groups 1 and 2.CONCLUSION:Topical administration of regorafenib 1mg/mL is partly effective for preventing alkali-induced corneal NV in rats.
文摘Background Currently, there are still divergent opinions about the mechanisms of the impaired neovascularization in diabetic subjects. Due to the remarkable therapeutic effect of angiotensin-converting enzyme inhibititors （ACEIs） on the reduction of blood pressure and the protection of target organs, the clinical application of this kind of drugs is very widespread. However, it is still not clear about the role and related molecular pathway of this kind of drugs in the limbs＇ postischemic revascularization. It is of major therapeutic importance to resolve these questions. This study aimed to investigate the reasons of the impaired angiogenesis in the hind limbs of rats with diabetic ischemia, the role and related molecular mechanisms of ACEI in postischemic revascularization. Methods Hind limbs ischemia was induced in diabetic rats by right femoral artery excision. Diabetic rats were randomly allocated to one of the following treatments for 4 weeks： ACEI by perindopril; perindopril in combination with a nitric oxide synthase （NOS） inhibitor; perindopril in combination with bradykinin （BK）-B1 receptor （BIR） antagonist or saline. The differences of angiogenesis, the mRNA and protein expression of endothelial nitric oxide synthase （eNOS）, vascular endothelial growth factor （VEGF） and basic fibroblast （bFGF）, constitutive nitric oxide synthase （cNOS） activity and nitric oxide （NO） content were observed after treatment. Results In non-ischemic hind limbs, no significant changes in capillary density, or the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity were observed among all groups. On the contrary, in ischemic hind limbs, the capillary density in diabetic rats decreased by 27% when compared with the control rats, so did the mRNA and protein expression of eNOS, VEGF and bFGF, or the NO content and the cNOS activity （P 〈0.05）. The capillary density was increased by 1.65-fold in the perindopril treatment group in reference to unt
