CPU86017及其旋光异构体对抗异丙肾上腺素对小鼠心肌的损害作用

Protection of mice myocardial tissues from isoproterenol-induced injury with CPU86017 and its optical isomers

目的:比较口服给CPU86017(对氯卞基四氢小檗碱)及其C-13a旋光异构体(SR和SS)对抗异丙肾上腺亲(ISO)所致小鼠心肌损害作用。方法:连续皮下注射ISO(1 mg·kg^(-1))10 d建立心肌肥厚模型,在d5～d10各治疗组分别灌胃给予普萘洛尔(5 mg·kg^(-1))、CPU 86017(40 mg·kg^(-1)),SR+SS(40 mg·kg^(-1))和SS(40 mg·kg^(-1))。末次给药24 h后取血处死小鼠。测定心重指数(全心重量/体重)和左心室重量指数(左心室重量/体重);左心室匀浆中丙二醛(MDA)和超氧化物歧化酶(SOD)活力;血清中谷草转氨酶(AST)、肌酸激酶(CK)、乳酸脱氢酶(LDH)活力。结果:CPU86017及SR,SS异构体均可显著逆转ISO模型组升高的心重指数,心肌中过度增加的MDA水平及降低的SOD活力,并显著降低血清中升高的AST,CK和LDH水平,其治疗效果与普奈洛尔相当。结论: CPU86017及其旋光异构体均明显对抗ISO所致的心肌肥大性损害作用。

Objective ： To assess if CPU86017 （p-chlorobenzyhetrahydroberberine chloride） and its optical isomers （3R ＆ SS） protect mice myocardial tissues from isoproterenol （ISO）-induced myocardial injury. Methods： A model of mice myocardial injury was produced by subcutaneously injecting ISO （1 mg·kg^-1） into mice myocardial tissues once daily for 10 days. The ISO-induced mice were randomly administered with one of four drug regimens： propranolol （5 mg· kg^-1, po） , CPU86017 （40 mg. kg^-1, po）, （SR ＋ SS） （40 mg· kg^-1, po） or SS （40 mg·kg^-1, po）. Additional healthy mice were used as normal control and ISO-induced mice as model control. Blood samples from the mice in 24 hours after the last administration of the drugs were collected to measure serum levels of AST, CK and LDH. The mice were then sacrificed under anesthesia to collect myocardial tissues for the measurements of heart weight index （ heart weight/body weight）, left ventricles （LV） weight index （ LV weight/body weight）, myo- cardial SOD activities and MDA level. Results： Compared to the normal control, the ISO-induced mice had heart hypertrophy, manifesting increments of heart and LV weight index as well as an exaggerated oxidative stress （SOD↓ and MDA ↑ in LV） and severe myocardial damage （ AST↑ , CK ↑ and LDH↑ in serum）. CPU86017 and its which s activitie ignificantly reversed opti the cal isomers worked on the ISO-induced heart tissues as propranolol did, ISO-induced heart index, abnormally higher MDA levels and less SOD s, and also reduced abnormally higher AST, CK and LDH levels. Conclusion： CPU 86017 and its optical isomers （SR ＆ SS） antagonized the ISO-induced mice heart injury.