Ishigooka Gaku, Mizuno Hiroshi, Oosuka Shou, Jin Denan, Takai Shinji, Kida Teruyo
Department of Ophthalmology, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Department of Innovative Medicine, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
J Clin Med. 2023 Oct 19;12(20):6627. doi: 10.3390/jcm12206627.
This study aimed to determine the role of oxidative stress produced by the renin-angiotensin system (RAS) in cataract formation in streptozotocin-induced diabetic rats (STZ) using angiotensin II receptor blockers (ARBs). Rats were treated with streptozotocin and orally administered candesartan (2.5 mg/kg/day) or a normal diet for 10 weeks until sacrifice. Cataract progression was assessed through a slit-lamp examination. Animals were euthanized at 18 weeks, and the degree of cataract progression was evaluated. Oxidative stress was also assessed. In STZ-treated rats, lens opacity occurred at 12 weeks. Cataract progression was inhibited in the ARB-treated group compared with the placebo group ( < 0.05). STZ-treated rats exhibited upregulated angiotensin-converting enzyme (ACE) gene expression than control rats. Oxidative stress-related factors were upregulated in the placebo-treated group but suppressed in the ARB-treated group. A correlation coefficient test revealed a positive correlation between ACE gene expression and oxidative stress-related factors and a negative correlation between ACE and superoxide dismutase. Immunostaining revealed oxidative stress-related factors and advanced glycation end products in the lens cortex of the placebo-treated group. The mechanism of diabetic cataracts may be related to RAS, and the increase in focal ACE and angiotensin II in the lens promotes oxidative stress-related factor production.
本研究旨在使用血管紧张素 II 受体阻滞剂(ARB)来确定肾素-血管紧张素系统(RAS)产生的氧化应激在链脲佐菌素诱导的糖尿病大鼠(STZ)白内障形成中的作用。用链脲佐菌素处理大鼠,并口服坎地沙坦(2.5 毫克/千克/天)或给予正常饮食,持续 10 周直至处死。通过裂隙灯检查评估白内障进展情况。在 18 周时对动物实施安乐死,并评估白内障进展程度。同时也评估了氧化应激情况。在接受 STZ 处理的大鼠中,12 周时出现晶状体混浊。与安慰剂组相比,ARB 处理组的白内障进展受到抑制(<0.05)。与对照大鼠相比,接受 STZ 处理的大鼠血管紧张素转换酶(ACE)基因表达上调。氧化应激相关因子在安慰剂处理组中上调,但在 ARB 处理组中受到抑制。相关系数检验显示 ACE 基因表达与氧化应激相关因子之间呈正相关,而 ACE 与超氧化物歧化酶之间呈负相关。免疫染色显示安慰剂处理组晶状体皮质中有氧化应激相关因子和晚期糖基化终产物。糖尿病性白内障的机制可能与 RAS 有关,晶状体中局部 ACE 和血管紧张素 II 的增加促进了氧化应激相关因子的产生。