补阳还五汤对脑缺血再灌注大鼠血小板PDK1/Akt Thr308通路的影响  

Effect of Buyanghuanwu Decoction preconditioning on platelet PDK1/Akt Thr308 pathway in acute cerebral ischemia reperfusion rats

作　　者：郑丽娴[1,2] 朱原[1] 徐愉林 秦莎莎[4] 姚晖[2] 张继平[1,2] 

机构地区：[1]南方医科大学中医药学院,广州510515 [2]南方医科大学附属佛山医院,佛山528000 [3]广东医科大学药学院,湛江524023 [4]广东药科大学中药学院,广州510515

出　　处：《中药药理与临床》2016年第4期1-4,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：广东省自然科学基金

摘　　要：目的:研究补阳还五汤预处理对急性脑缺血再灌注损伤大鼠血小板蛋白PDK1、Akt Thr308的影响,初步探讨补阳还五汤抗血小板活化作用与PDK1/Akt Thr308信号通路的关系。方法:用不同剂量补阳还五汤(29.69、14.84、7.42 g/kg)及硫酸氢氯吡格雷(7.81×10^(-3)mg/kg)分别ig预处理大鼠,模型组、假手术组及空白组给予蒸馏水ig,1天/次,连续14天。14天后采用线栓法建立大鼠大脑中动脉栓塞(MCAO)再灌注损伤模型,缺血2h再灌注6h后进行神经功能缺损评分及脑组织TTC染色,流式细胞术(FCM)检测全血中血小板CD62P含量,Western blot检测富血小板血浆(PRP)中PDK1、Akt Thr308蛋白磷酸化水平。结果:与假手术组比较,模型组血小板CD62P显著增高;与模型组比较,补阳还五汤组(29.69、14.84、7.42 g/kg)及硫酸氢氯吡格雷组(7.81×10^(-3)mg/kg)均明显降低血小板CD62P的表达;与假手术组比较,模型组PDK1、Akt Thr308蛋白磷酸化水平显著升高,而补阳还五汤组(29.69、14.84、7.42 g/kg)及硫酸氢氯吡格雷组(7.81×10^(-3)mg/kg)PDK1、Akt Thr308蛋白磷酸化水平明显低于模型组。结论:补阳还五汤预处理可降低急性脑缺血再灌注损伤大鼠血小板CD62P含量,并降低PDK1、Akt Thr308蛋白磷酸化水平,提示补阳还五汤可能通过抑制PDK1/Akt Thr308信号通路发挥抗血小板活化作用。Objective：To investigate the effect of Buyanghuanwu Decoction （BHD） preconditioning on platelet proteins PDK1 and Akt Thr308 in a- cute cerebral ischemia reperfusion rats, which is to explore the relationship between the mechanism of BHD anti-platelet activation and PDK1/ Akt Thr308 signaling pathway. Methods： Rats were given by gavage with different dosage of BHD （29.69,14.84,7.42g/kg） and clopi- dogrel（ 7. 81 × 10^-3mg/kg） . model group（ MG）, sham operation group（SG） ,blank group（BG） were given by garage with distilled water, once a day for 14 days. The rat model of occlusion of the middle cerebral artery（MCAO） reperfusion was established ;vith an intraluminal sili- con-coated filament at day 14. Then after 2 hours of middle cerebral artery occlusion and 6 hours reperfusion,the nervous function deficit scores was evaluated and brain tissue was stained with TTC. Platelet CD62P in whole blood and the phosphorylation level of PDK1 and Akt Thr308 proteins in platelet rich plasma were studied by flow eytometry（FCM） and western blot（WB） as well,respectively. Results： Compare with SG, platelet CD62P was significantly increased in MG （ P 〈 0.01 ） ; Compare with MG, BHD groups （29.69,14.84,7.42g/kg） and clopi- dogrel group（7.81 × 10^ -3mg/kg） significantly decreased the expression of platelet CD62P（ P 〈0.01 ） ;Compare with SG,The phosphorylation level of PDK1 and Akt Thr308 proteins in MG was significantly improved（ P 〈 0.01 ）. However, BHD groups （29.69,14.84,7.42g/kg） and clopidogrel group （7.81× 10^-3 mg/kg） were obviously lower than MG （ P 〈 0.05 or P 〈 0.01 ）. Conclusion： Buyanghuanwu Decoction precon- ditioning could decrease the expression of platelet CD62P and the phosphorylation level of proteins PDK1 and A.kt Thr308 in acute cerebral is- chemia reperfusion rats, which reveals that BHD could inhibit PDK1/Akt Thr308 signaling pathway to anti-platelet activation.

关 键 词：补阳还五汤 急性脑缺血再灌注损伤 抗血小板活化 CD62P PDK1/Akt Thr308 

分 类 号：R285.5[医药卫生—中药学]