CDR132L 改善高血压合并高脂血症小鼠血管重构和功能.

Aim To investigate the effect of CDR132L (miR-132 antisense oligonucleotide) on vascular remodeling and function in mice with hypertension and hyperlipidemia, and explore its possible mechanism. Methods A total of 30 8-week-old male C57BL/6 mice were randomly divided into three groups: control group, model group and CDR132L group, with 10 mice in each group. The control group received with a standard diet while the model group and CDR132L group received N-nitro-L-arginine methyl ester (L-NAME) and high-fat diet to induce hypertension and hyperlipidemia. The CDR132L group was administered with intraperitoneal injection of CDR132L at a dose of 20 mg/kg once weekly for six consecutive weeks, whereas the control group and the model group were given intraperitoneal injection of an equivalent volume of normal saline. The tail-cuff method was utilized for blood pressure measurement, blood lipid and glucose levels were assayed by an automatic biochemical analyzer, the thoracic aorta structure was observed by HE staining, endothelium-dependent relaxation of the thoracic aorta was evaluated by the vascular ring test, the expression level of miR-132 in the thoracic aorta was measured by qPCR, the protein expression levels of Gab1 and endothelial nitric oxide synthase (eNOS) in the thoracic aorta were determined by Western blot. Results Compared with the control group, the model group demonstrated notable rises in systolic and diastolic blood pressure, serum triglyceride, total cholesterol levels, and body weight. Moreover, the intima of thoracic aorta and the thickness of vascular wall was uneven, the smooth muscle cells of the tunica media were arranged irregularly, with a large amount of fat deposition in the vascular wall, and the endothelium-dependent relaxation response of thoracic aorta was decreased (P<0. 05). The expression level of miR-132 in the thoracic aorta was significantly increased (P<0. 05), while the expression level of Gab1 and eNOS protein was markedly decreased (P<0. 05). Compared with the model group, the CDR132L group showed no significant differences in systolic and diastolic blood pressure, serum triglyceride and total cholesterol levels, as well as body weight (P>0. 05). However, the CDR132L group exhibited a complete and smooth intima of the thoracic aorta with minimal intravascular lipid deposition, the thickness of the vascular wall was uniform, the smooth muscle cells of the tunica media were arranged orderly, accompanied by enhanced endothelium-dependent relaxation response of the thoracic aorta (P<0. 05). The expression level of miR-132 in the thoracic aorta was significantly decreased (P <0. 05), while the expression levels of Gab1 and eNOS protein were significantly increased (P<0. 05). Conclusion CDR132L can improve vascular remodeling and endothelium-dependent relaxation in hypertensive and hyperlipidemia mice, which may be related to the decrease of miR-132 expression level and the up-regulation of Gab1 and eNOS protein expression levels in the thoracic aorta. [ABSTRACT FROM AUTHOR]