Effects Of Melatonin And Cilazaprilil On Cellular Apoptosis In Basal Forebrain And Hippocampus And Memory Of Renal Hypertensive Rats

Objective:To investigate the effects of melatonin and cilazapril on the change in memory, Bax/Bcl-2 protein and cellular apoptosis in basal forebrain(nucleus basalis of Meynert ; vertical limb of diagonal band of Broca,vDB)and hippocampal subdivisions(CA1,CA3)of renal hypertensive rats.Methods: Healthy adult Sprague-Dawley rats were randomly divided into following four groups with ten rats in each group: sham, renovascular hypertensive plus vehicle treatment, renovaseular hypertensive plus melatonin treatment, renovaseular hypertensive plus cilazapril treatment. After the renal hypertension model was established, the four group rats received corresponding treatments, and blood pressure was measured accordingly. Learning and memory were detected in Morris water maze. Bcl-2/Bax protein or apoptotic cells in the above brain areas were examined by immunohistochemistoy or by TUNEL technique.Results: The number of Bax immunoreactive (Bax-IR)cells and apoptotic cells in basal forebrain and hippocampal subdivisions increased significantly (p<0.05),but the ratio of Bcl-2/ Bax and the ability of learning and memory significantly decreased in renovascular hypertensive group rats, compared with those of sham operation group (p<0.05). Comparing with those of renovascular hypertensive plus vehicle treatment, the blood pressure and the number of Bax-IR cells and apoptotic cells significantly decreased (p<0.05), the ratio of Bcl-2/ Bax and the ability of learning and memory also significantly increased (p<0.05) in renovaseular hypertensive plus cilazapril treatment. Compared with those of renovascular hypertensive plus vechicle treatments rats, the blood pressure decreased slightly in melatonin-treated group, but was significantly higher than that of renovascular hypertensive plus vichicle or cilazapril treatment rats (p<0.05), the number of Bax-IR cells of metatonin group was not significantly different from that of renovascular hypertensive group(p>0.05). However, the number of Bcl-2-IR cells and the ratio of Bcl-2/ Bax in cilazapril-treated group significantly increased, while the number of apoptotic cells was significantly decreased, but the ability of learning and memory of the cilazapril group increased (p<0.05).Conclusions:The blood pressure may be adjusted to normal level,and the imbalance of the ratio of Bcl-2/ Bax is corrected by cilazapril, which leads to lowering the number of apoptosis cells, improving the impaired ability of learning and memory. Blood pressure slightly is affected, and the protein expression of Bax and Bcl-2, is regulated by melatonin,which results in proventing excessive apoptosis, and retifying impaired of learning and memory of hypertensive rats.