【摘要】 目的观察avastin全身用药对视网膜新生血管的抑制作用及其对肾脏的损伤。方法选择7日龄SD大鼠60只分为空气对照组、高氧对照组、高氧NS(生理盐水)组和avastin大、中、小剂量给药组,各10只。空气对照组不予处理。其余50只大鼠置于80%高氧环境中连续生活5d,建立高氧诱导的SD大鼠血管增生性视网膜病变模型。药物治疗组尾静脉分别给予浓度为15.625,31.25,62.5 mg/kg的avastin 0.1ml,高氧NS组尾静脉给予生理盐水0.1ml,高氧对照组不给予处理。通过视网膜铺片和视网膜组织切片HE染色观察avastin对新生血管的抑制作用,通过肾脏病理切片HE染色来观察其形态学变化。结果高氧对照组与空气对照组相比,视网膜有大量新生血管形成,结构及分布紊乱,高氧诱导的血管增生性视网膜病变动物模型诱导成功;药物治疗组与高氧NS组相比视网膜血管分布较规则、密度减少,且突破视网膜内界膜的血管内皮细胞核数目明显减少(P<0.01),药物治疗三组间比较也有统计学意义(均P<0.05)。肾脏病理切片显示,高氧对照组和高氧NS组与空气对照组相比,肾小管上皮细胞变性、坏死,小管基底膜断裂;中、小剂量给药组肾小球系膜轻度增生,间质炎性细胞浸润;大剂量给药组肾小球细胞数目增多,间质轻度细胞增生。结论avastin全身用药对视网膜新生血管具有抑制作用,并且随着给药剂量的增加,抑制作用更加明显。中、小剂量给药可引起轻度肾脏损伤,大剂量给药肾脏损伤稍重。更多还原

【Abstract】 Objective To explore inhibitive effect of systemic avastin therapy on retinal neovascularization and the damage of kidney. Methods Sixty 7-day-old SD rats were divided into six groups:air control group(n=10),hyperxia control group(n=10),hyperxia NS group(n=10),avastin groups(high,medium,low dosage groups).SD rats in air control group were not given any treatment.The other fifty rats were put into the environment with 80% oxygen for 5 d to establish models of retinal neovascularization.Then 40 SD rats were given different concentrations of 15.625,31.25,62.5 mg/kg avastin 0.1 ml and NS 0.1 ml in the tail vein in avastin groups and in hyperxia NS group,respectively.The inhibition of angiogenesis was observed by the retinal flat and HE staining,and pathological changes of kidney were observed by HE staining. Results Compared with air control group,there was large retinal new vessels in hyperxia control group,and the density and shape of retinal neovascularization were in disorder.The animal model of oxygen-induced retinopathy with vascular proliferation was successfully established.Compared with hyperxia NS group,retinal new vessels was distributed regularly in avastin treatment groups,its density decreased,and the numbers of the endotheliocyte nuclei of new vessels extending to layer of retina decreased(P<0.01).And there was significant difference between the three avastin groups(P<0.05).Renal tubular epithelial cell degeneration and necrosis,the basement membrane fracture were found in hyperxia control group,hyperxia NS group.Mild mesangial hyperplasia,interstitial infiltration of inflammatory cells were observed in medium and low dosage groups.The numbers of glomerular cells increased,and stromal cells were mild hyperplasied in high dosage group. Conclusion Systemic avastin therapy could inhibit retinal neovascularization in rats in a dose-dependent manner.The medium and low dosage of avastin could have a mild damage to kidney,but the high dosage could cause more serious injury.更多还原