慢性肾衰大鼠脑组织线粒体呼吸功能变化及氯沙坦的干预

目的：研究慢性肾功能衰竭（chronic renal failure，CRF）模型大鼠脑组织线粒体呼吸功能和细胞凋亡相关蛋白质的变化，并探讨氯沙坦的干预作用。方法：雄性SD大鼠24只，随机分为假手术组（Sham）、病理组（Nx）和氯沙坦干预组（Lst），行5/6肾切除手术，建立慢性肾衰模型，Lst组于饮水中给予氯沙坦（50 mg·L-1）治疗。给药结束后，测定SCr、BUN水平及脑组织MDA的含量和SOD的活性，氧电极法检测脑组织线粒体呼吸3态氧耗率（ST3）、4态氧耗率（ST4）和呼吸控制率（RCR），免疫印迹法观察Caspase-3、Cleaved caspase-3、Cleaved caspase-9、Bcl-2蛋白表达变化。结果：与Sham组相比，Nx组SCr、BUN含量显著升高（P<0.01），MDA含量显著升高（P<0.01），SOD活性显著下降（P<0.01），ST3、RCR显著降低（P<0.01），ST4显著升高（P<0.05），Cleaved caspase-3、Cleaved caspase-9蛋白水平显著升高（P<0.01、P<0.05），Caspase-3、Bcl-2蛋白水平显著降低（P<0.01）。与Nx组相比， Lst组SCr、BUN含量显著降低（P<0.01），MDA含量显著下降（P<0.01），ST3、RCR显著升高（P<0.01），Cleaved caspase-3、Cleaved caspase-9蛋白水平明显降低（P<0.01），Caspase-3、Bcl-2蛋白水平明显升高（P<0.01）。结论：慢性肾衰可造成大鼠脑组织氧化损伤，损害线粒体呼吸功能，促进神经细胞凋亡。氯沙坦通过减轻氧化应激损伤，改善线粒体呼吸功能，减少细胞凋亡，发挥神经保护作用。

Changes of mitochondrial respiratory function in brain of chronic renal failure rats and intervention with losartan

Objective: To observe the changes of mitochondrial respiratory function and the expression of apoptosis-related proteins and explore the interventional effect of losartan on these changes in the brain tissues of chronic renal failure rats. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into Sham group (Sham, n=8), pathology group of chronic renal failure (Nx, n=8) and losartan group (Lst, n=8). The rat model of chronic renal failure was established by 5/6 nephrectomy. Rats of Lst group were given losartan (50 mg·L-1) through drinking water in the 7th and 8th weeks after nephrectomy. Then changes in brain mitochondrial respiratory state 3 (ST3), state 4 (ST4) and respiratory control rate (RCR) were determined by oxygen electrode, and the expression of Caspase-3/Cleaved caspase-3, Cleaved caspase-9 and bcl-2 were detected by Western blot. The serum creatinine (SCr) and blood urea nitrogen (BUN), malonaldehyde (MDA) and superoxide dismutase (SOD) of brain were also measured. Results: Compared with the Sham group, the mitochondrial RCR and the expression of Caspase-3 and Bcl-2 were significantly decreased (P<0.01), while the expression of Cleaved cas-pase-3, Cleaved caspase-9 and the content of MDA were significantly increased ( P<0.01, P<0.05). Losartan sig-nificantly raised RCR and the expression of caspase-3 and Bcl-2 (P<0.01) and reduced the expression of Cleaved caspase-3 and Cleaved caspase-9 and the content of MDA (P<0.01). Conclusion: Chronic renal failure may induce oxidant damage and mitochondrial respiratory dysfunction in rat brains, leading to neuronal apoptosis. Losartan could protect neurons against these injuries.