Yang Fang, Wang Jindong, Li Fei, Cui Lei
Department of Cardiology, Yantaishan Hospital, Yantai, Shandong Province, China.
Department of General Surgery, Yeda Hospital, Yantai, Binzhou Medical College, Shandong Province, China.
Exp Clin Endocrinol Diabetes. 2016 Jun;124(6):367-71. doi: 10.1055/s-0042-104496. Epub 2016 Jun 21.
Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated.
Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment.
No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy.
Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy.
内源性一氧化氮（NO）有助于抑制Rho相关激酶2（ROCK2）的表达。然而，外源性NO对ROCK2表达的影响鲜少被研究。
制备血脂异常的兔子，并随机分为未治疗组、阿托伐他汀组、硝酸甘油组和联合治疗组（每组n = 10）。药物治疗持续2周。在基线、血脂异常建立2周和药物治疗2周时评估包括血脂谱、肝酶、C反应蛋白（CRP）、丙二醛（MDA）、NO水平和ROCK2水平等相关参数。
各组在基线时参数无显著差异。血脂异常建立2周后，与基线相比，血脂谱、CRP和MDA的血清水平显著升高。此外，还观察到NO生成减少和ROCK2表达增强。药物治疗2周后，阿托伐他汀组和联合治疗组的血脂谱、全身炎症（以血清CRP水平反映）和氧化（以血清MDA水平反映）得到改善，但硝酸甘油组未改善（P < 0.05）。此外，阿托伐他汀组和硝酸甘油组均观察到NO生成增加伴随ROCK2表达降低，联合治疗进一步增强了这些益处（P < 0.05）。药物治疗2周后未观察到肝酶升高。
硝酸甘油衍生的外源性NO可有效抑制血脂异常兔子的ROCK2表达，这与脂质修饰无关，他汀类药物治疗可增强这些疗效。
