论文部分内容阅读
目的:观察柿叶黄酮对KKAy小鼠糖尿病视网膜病变(DR)结缔组织生长因子(connective tissue growth factor,CTGF),血管内皮生长因子(vascular endothelial growth factor,VEGF),以及低氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)的影响及其保护机制。方法:取30只8周龄C57BL6/J小鼠作为正常组,另取150只8周龄雄性KKAy小鼠随机分为KKAy模型组、柿叶黄酮高、中、低剂量组、羟苯磺酸钙组,每组各30只小鼠。柿叶黄酮高、中、低剂量组分别给予柿叶黄酮(50,100,200 mg·kg~(-1)·d~(-1))ig,羟苯磺酸钙组给予羟苯磺酸钙230 mg·kg~(-1)·d~(-1)ig,KKAy模型组及正常组给予等量生理盐水灌胃,共16周。检测血糖(FBG),糖化血红蛋白(GHb),血液流变学指标;酶联免疫吸附测定(ELISA)法检测法检测视网膜内CTGF,VEGF,蛋白质免疫印迹(Western blot)法检测HIF-1α的表达。苏木素-伊红(HE)染色观察视网膜组织损伤情况,TUNEL检测视网膜细胞凋亡程度。结果:与正常组小鼠比较,KKAy模型组小鼠的血糖显著升高,GHb的水平显著降低(P<0.01),视网膜CTGF,VEGF和HIF-1α的表达显著增加(P<0.01),视网膜组织结构损伤严重。经过16周给药,与KKAy模型组比较,柿叶黄酮中、高剂量组小鼠的血糖显著降低(P<0.01),GHb的水平显著提高(P<0.01),视网膜CTGF,VEGF和HIF-1α的表达及明显减少(P<0.05,P<0.01),视网膜组织损伤情况改善明显。结论:柿叶黄酮对KKAy小鼠DR具有保护作用,其机制可能与调节视网膜内CTGF,VEGF和,HIF-1α的表达有关。
Objective: To observe the effects of persimmon leaf flavonoids on connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) and hypoxia in diabetic retinopathy (DR) -inducible factor-1α, HIF-1α) and its protective mechanism. Methods: Thirty 30-week-old C57BL6 / J mice were used as normal group. Another 150 KKAy mice of 8 weeks old were randomly divided into KKAy model group, high, medium and low dose of persimmon leaf flavone, Calcium group, 30 mice each. Persimmon leaf flavonoids were given high, medium and low doses of persimmon leaf flavonoids (50,100,200 mg · kg -1 · d -1) ig, calcium dobesilate group given calcium dobesilate 230 mg · kg ~ (-1) · d ~ (-1) ig, KKAy model group and normal group were given the same amount of saline for 16 weeks. (FBG), glycated hemoglobin (GHb) and hemorheology indexes were detected. CTGF and VEGF in the retina were detected by enzyme linked immunosorbent assay (ELISA), and the expression of HIF-1α was detected by Western blot . The damage of retinal tissue was observed by hematoxylin-eosin (HE) staining and the apoptosis of retinal cells was detected by TUNEL. Results: Compared with the normal group, the blood glucose of KKAy model group was significantly increased, the GHb level was significantly decreased (P <0.01), the expression of CTGF, VEGF and HIF-1α in retina was significantly increased (P <0.01) Severe tissue damage. After 16 weeks of administration, compared with KKAy model group, the blood glucose of the middle and high dose of persimmon leaf flavonoids decreased significantly (P <0.01), the level of GHb increased significantly (P <0.01), the expression of CTGF, VEGF and HIF- 1α expression and significantly decreased (P <0.05, P <0.01), retinal tissue injury improved significantly. Conclusion: Persimmon leaf flavonoids can protect DR in KKAy mice, and its mechanism may be related to the regulation of CTGF, VEGF and HIF-1α expression in the retina.