Yang Y, Yang J, Jiang Q
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
Transplant Proc. 2014 Jun;46(5):1573-7. doi: 10.1016/j.transproceed.2014.01.018.
Nowadays, hepatic ischemia reperfusion (HI/R) injury is regarded as a serious concern in clinical practices. Huperzine A (HupA) is an alkaloid isolated from the Chinese folk medicine huperzia serrate, which has possessed diverse pharmacological actions.
A mouse model of HI/R was caused by clamping the hepatic artery, the hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The sham group experienced the identical procedure without hepatic ischemia. The HupA group received an injection into the tail vein 5 minutes prior to HI/R at the doses of 167 and 500 μg/kg. The vehicle group was injected with physiological saline instead of HupA. The liver function was assessed by determinations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Tissue levels of superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and glutathione (GSH) were also measured spectrophotometrically. In addition, the activities of hepatic inflammatory mediators such as nuclear factor kappa B (NF-κB) p65, tumor necrosis factors-α (TNF-α, interleukin-1β (IL-1β) and IL-6 were also measured. Furthermore, the apoptotic damage was evaluated by measuring caspase-3 activity in hepatic tissues.
Treatment with HupA in mice at the doses of 167 and 500 μg/kg remarkably reduced serum ALT and AST activities in HupA-treated ischemic mice. Furthermore, HupA treatment could enhance the activities of hepatic tissue SOD, CAT, and GSH but decrease MDA tissue content. The activities of inflammatory cytokines including NF-κB p65, TNF-α, IL-1β and IL-6 were all decreased in ischemic mice treated with HupA. Colorimetric test results illustrated that a marked reduction of caspase-3 activity was found in the HupA-treated group compared with the vehicle group.
Our present data suggest that HupA has a protective role against HI/R injury of mice and antioxidative, anti-inflammatory, and antiapoptotic actions are involved in its protection.
如今，肝缺血再灌注（HI/R）损伤在临床实践中备受关注。石杉碱甲（HupA）是从中国民间草药蛇足石杉中分离出的一种生物碱，具有多种药理作用。
通过在麻醉状态下用血管夹夹闭肝动脉、肝门静脉和胆管30分钟，随后再灌注6小时，建立HI/R小鼠模型。假手术组经历相同的操作，但无肝缺血。HupA组在HI/R前5分钟经尾静脉注射，剂量分别为167和500μg/kg。载体组注射生理盐水而非HupA。通过测定丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）活性评估肝功能。还采用分光光度法测定组织中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、丙二醛（MDA）和谷胱甘肽（GSH）的水平。此外，还测定了肝炎症介质如核因子κB（NF-κB）p65、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和IL-6的活性。此外，通过测量肝组织中半胱天冬酶-3活性评估凋亡损伤。
167和500μg/kg剂量的HupA治疗显著降低了HupA处理的缺血小鼠血清ALT和AST活性。此外，HupA治疗可增强肝组织SOD、CAT和GSH的活性，但降低MDA组织含量。在接受HupA治疗的缺血小鼠中，包括NF-κB p65、TNF-α、IL-1β和IL-6在内的炎性细胞因子活性均降低。比色试验结果表明，与载体组相比，HupA治疗组中半胱天冬酶-3活性显著降低。
我们目前的数据表明，HupA对小鼠HI/R损伤具有保护作用，其保护作用涉及抗氧化、抗炎和抗凋亡作用。
