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背景原发性高血压(EH)易造成视网膜血管损伤,伴随有血管内皮细胞凋亡。有研究表明血管紧张素Ⅱ(AngⅡ)能够通过其受体诱导血管内皮细胞发生凋亡,氯沙坦减少高血压靶器官对AngⅡ的反应,降低外周阻力、改善血管重构,对心血管系统起到有利的作用,但氯沙坦是否能逆转高血压视网膜病变中微血管的形态和功能,是否减少视网膜微血管凋亡现在仍不清楚。目的观察自发性高血压大鼠(SHR)视网膜毛细血管形态,研究氯沙坦对SHR视网膜毛细血管细胞凋亡的作用。方法将12周龄雄性SHR随机分成SHR氯沙坦组[氯沙坦30 mg/(kg.d),灌胃,n=10]与对照组(对照组,n=10),另设12周龄雄性Wistar-Kyoto大鼠作正常对照组(WKY,n=10)。实验前及实验开始后测大鼠鼠尾动脉收缩压1次/4周。饲养8周后,采用透射电镜、视网膜消化铺片的HE染色、原位DNA末端酶标记技术(TUNEL)和免疫组化法检测视网膜毛细血管细胞凋亡情况。结果氯沙坦能显著降低SHR的收缩压,显著降低视网膜毛细血管细胞凋亡率[SHR组(28.9±7.2)%比氯沙坦组(7.3±5.5)%比WKY组(2.4±1.9)%,P<0.01],但仍未达到WKY组的水平(P<0.05)。电镜下对照组毛细血管周细胞有早期凋亡表现,内皮细胞核轻度异常,氯沙坦组未见异常。氯沙坦减轻SHR bax的表达(P<0.01),增加bcl-2但未能达到WKY大鼠水平(P>0.05)。结论氯沙坦不仅有明显的降压作用,而且在高血压病程中可抑制视网膜毛细血管内皮细胞和周细胞凋亡。
Background Essential hypertension (EH) can easily lead to retinal vascular injury, accompanied by vascular endothelial cell apoptosis. Studies have shown that angiotensin Ⅱ (Ang Ⅱ) can induce apoptosis of vascular endothelial cells through its receptor, losartan to reduce the response of target organs of hypertension to Ang Ⅱ, reduce peripheral resistance, improve vascular remodeling, the cardiovascular system To the beneficial effect, but whether losartan can reverse the microvascular morphology and function in hypertensive retinopathy, whether to reduce retinal microvascular apoptosis is still unclear. Objective To observe the morphology of retinal capillaries in spontaneously hypertensive rats (SHR) and investigate the effect of losartan on apoptosis of retinal capillary cells in SHR. Methods SHRs of 12-week-old male SHR were randomly divided into three groups: losartan group (losartan 30 mg / (kg.d), gavage n = 10] and control group (n = 10) Age male Wistar-Kyoto rats as normal control group (WKY, n = 10). The rat tail artery systolic pressure was measured 1/4 weeks before and after the start of the experiment. After 8 weeks of feeding, the apoptosis of retinal capillary cells was detected by transmission electron microscopy, HE staining of retina digestion, enzymatic in situ DNA labeling (TUNEL) and immunohistochemistry. Results Losartan significantly reduced SHR systolic pressure and significantly decreased retinal capillary cell apoptosis [(28.9 ± 7.2)% in SHR group compared with (7.3 ± 5.5)% in losartan group and (2.4 ± 1.9)% in WKY group , P <0.01], but still not reached the level of WKY group (P <0.05). Under the electron microscope, there were early apoptosis of capillary pericytes in control group, mild abnormality of endothelial cell nucleus and no abnormality in losartan group. Losartan reduced the expression of SHR bax (P <0.01), increased bcl-2 but failed to reach the level of WKY rats (P> 0.05). Conclusion Losartan not only has obvious antihypertensive effect, but also inhibits the apoptosis of retinal capillary endothelial cells and pericytes during the course of hypertension.