动物造模 z-bio 2022-07-05 313

　　Objective To investigate the promoting effect of microRNA-328 (miR-328) in improving the expression of L-type voltage-gated calcium channel in thoracic aortic smooth muscle cells of hypertensive rats by aerobic exercise.

　　Methods 12-week-old male normotensive rats (Wistar Kyoto, WKY) and spontaneously hypertensive rats (spontancously hypertensive at, SHR) were randomly divided into normotensive control group (WKY-C) and normotensive exercise group (WKY- EX), hypertension control group (SHR-C), hypertensive exercise group (SHR-EX), and exercise group underwent 12 weeks of moderate-intensity treadmill training. After 12 weeks, femoral arteriovenous catheterization was used to detect the cardiovascular response of the rats; the thoracic aorta of the rats was taken, the morphology of the thoracic aorta was detected by HE staining, and the expression of LTCCα, β, subunit mRNA and miR-328 was detected by qPCR. Bloa detects alpha, and beta, subunit protein expression. In vitro experiments, WKY thoracic aortic smooth muscle cells were cultured, miR-328mimic and miR-328 ihibior were overexpressed or silenced by liposome transfection, and the changes of LTCCαc and β, subunit mRNA and protein expressions were detected.

　　Results (1) Aerobic exercise can significantly reduce SHR body weight, blood pressure and heart rate; (2) Exercise can significantly reduce SHR thoracic aortic wall thickness; (3) Exercise can significantly reduce SHR's vasopressor response to norepinephrine and nitrate. The antihypertensive response of Nifcdipine (LTCC blocker); (4) The mRNA and protein expressions of LTCCαn and β, subunits in the SHR-C group were significantly higher than those in the WKY-C group, while the α, c and β, subunit mRNA and protein expressions were significantly lower than those in the SHR-C group; (5) The expression of miR-328 in the SHR-C group was significantly lower than that in the WKY-C group, and the expression of miR-328 was significantly increased after 12 weeks of aerobic exercise ;(6) In the in vitro experiments, compared with the control group, the mRNA and protein expressions of α, β, subunits in the transfected miR-328 mimice group were significantly down-regulated, while the α, and β, subunits in the transfected miR-328 inhibitor group were significantly down-regulated. The expression of basal mRNA and protein was significantly up-regulated.

　　Conclusion Regular aerobic exercise can effectively reduce SHR blood pressure, regulate miR-328 to target and inhibit the expression of LTCCα, and β, subunits, which may be one of the mechanisms by which exercise improves LTCC remodeling in hypertensive thoracic aorta.