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Protective effect of bilobalide on myocardial ischemia/reperfusion injury of rats via anti-inflammation and anti-oxidation / 中国药理学与毒理学杂志
Chinese Journal of Pharmacology and Toxicology ; (6): 241-249, 2019.
Article in Chinese | WPRIM | ID: wpr-857539
ABSTRACT
OBJECTIVE To investigate the effects of bilobalide (BB) on the myocardial tissue of rats with myocardial ischemia/reperfusion (Ml/R). METHODS An Ml/R model was prepared by ligating the anterior descending branch of the left coronary artery in rats for 30 min. BB 2, 4 and 8 mg-kg"1 was adminsterted for four weeks. The heart rate of rats was recorded and myocardial infarction area was detected. Detective kits were used to evaluate the concentrations of creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH). HE staining was performed to observe the myocardial injury, and TUNEL staining was performed to evaluate apoptosis. ELISA was performed to determine the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), IL-1p, tumor necrosis factor-a (TNF-a) and IL-10. Immunohistochemistry was performed to evaluate the expressions of Ki67 and interleukin-6 (IL-6). Western blotting was performed to evaluate the expressions of Bcl-2, Bax, cleaved-caspase 3, nuclear factor (erythroid-derived 2)-like 2 protein (Nrf2), heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQ01), NF-kB P65, phosphorylated inhibitor of NF-kB (P-IkBoc) and IkBcx kinase (p-IKK). RESULTS Compared with normal control group, the percentage of the myocardial infarction area and the concentration of CK-MB and LDH were increased in Ml/R model group, but heart rate was decreased (P<0.01) and myocardial tissue showed myocardial fiber rupture and inflammatory infiltration. Compared with Ml/R model group, the percentage of the myocardial infarction area and the concentration of CK-MB and LDH were decreased in Ml/R model+BB 2, 4 and 8 mg-kg"1 groups (P<0.05), but heart rate was increased (P<0.01) and myocardial tissue fibers tended to be regular while inflammatory cell infiltration was significantly reduced. Compared with normal control group, the percentage of apoptotic cells and Ki67 expression-positive cells and the expressions of Bax and cleaved-caspase 3 were increased in Ml/R model group (F<0.01), but the expression of Bcl-2 was decreased markedly (P<0.01). Compared with Ml/R model group, the percentages of apoptotic cells and Ki67 expression-positive cells and the expressions of Bax and cleaved-caspase 3 were decreased in Ml/R model+BB 2, 4 and 8 mg∗kg-1 groups (P<0.01), while the expression of Bcl-2 was increased (P<0.01). Ml/R could lower the activity of SOD and GSH-Px, but enhance MDA content. BB could weaken the effect of Ml/R on SOD, GSH-Px and MDA. Compared with normal control group, the concentrations of IL-1β, TNF-α and IL-10 in serum and the percentage of IL-6 expression-positive cells in myocardial tissue of Ml/R model group were increased (P<0.01). Compared with Ml/R model group, the concentrations of IL-1β and TNF-a and the percentage of IL-6 expression-positive cells were decreased in Ml/R model∗ BB 2, 4 and 8 mg-kg"1 group (P<0.01), but the concentration of IL-10 was increased(P<0.05). Compared with mormal control group, the protein levels of Nrf2, HO-1 and NQ01 significantly decreased (P<0.01), while the levels of NF-kB P65, p-IKK and p-kBa significantly increased (P<0.01). BB could effectively reverse protein changes (P<0.05, P<0.01). CONCLUSION BB can protect rats with Ml/R via anti-inflamma-tion and anti-oxidation.

Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Type of study: Prognostic study Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2019 Type: Article