常用几种肝病注射剂体外对血清胆碱酯酶活性影响的实验研究

作者;郭献忠,梁学琳,颜剑斌,王治宇,苏 毅,李晓琳,金树根。

[摘要] 目的 通过观察常用几种肝病注射剂体外对血清胆碱酯酶活性作用来评价其可能的生物学意义。方法 采用高、低剂量茵栀黄、清开灵甘利欣、香丹、柴胡、葛根素、穿琥宁、醒脑净、鱼腥草及肝炎灵注射液体外与血清共孵育10min和24h,观察其对血清胆碱酯酶活性的影响。结果 高、低剂量的肝炎灵注射液血清作用10min和24h均致胆碱酯酶活性明显下调,而高、低剂量的柴胡、葛根素、穿琥宁、醒脑净、鱼腥草等注射液血清作用10min和24h均致胆碱酯酶活性上调。高剂量茵栀黄、清开灵甘利欣、香丹注射液和低剂量茵栀黄、清开灵注射液血清作用24h致胆碱酯酶活性有下调趋势,而低剂量甘利欣、香丹注射液血清作用24h致胆碱酯酶活性下调。结论 肝炎灵注射液胆碱酯酶活性有明显下调作用,可能与其神经系统毒性(烟碱样中毒症状)有关,柴胡、葛根素、穿琥宁、醒脑净、鱼腥草注射液则有上调作用,而甘利欣、香丹注射液胆碱酯酶活性下调作用较慢而弱,其临床意义有待进一步研究。 [关键词] 中药;血清;体外;胆碱酯酶活性 Effects of some commonly used injectable preparations for liver diseases on serum cholinesterase activity in vitro [Abstract] Objective To observe in vitro effects of some commonly used injectable preparations for liver diseases on serum cholinesterase activity and explore the mechanism.Methods The high and low dose of these of injections such as Yinzhihuang,Qingkailing,Diammonium Glycyrrhizinate,Xiangdan,Chaihu,Puerarin,Chuanhuning,Xingnaojing,Yuxingcao and Ganyanlin were incubated with serum in vitro for 10 minutes and 24 hours,serum cholinesterase activity was measured.Results By in vitro incubating with serum for 10 minutes and 24 hours,the high and low dose of Ganyanlin upregulated cholinesterase activity significantly,and those of Chaihu,Puerarin,Chuanhuning,Xingnaojing and Yuxingcao downregulated cholinesterase activity.Only by in vitro incubating with serum for 24 hours,the high dose of Yinzhihuang,Qingkailing,Diammonium Glycyrrhizinate,Xiangdan and low dose of Yinzhihuang,Qingkailing downregulated cholinesterase activity insignificantly,but the high dose of Diammonium Glycyrrhizinate and Xiangdan downregulated cholinesterase activity.Conclusion In vitro Ganyanlin downregulates the serum cholinesterase activity directly and significantly,and the effect may be related to its nerve system tocixity.In vitro Chaihu,Puerarin,Chuanhuning,Xingnaojing and Yuxingcao upregulate the serum cholinesterase activity directly,and the downregulative effects of Diammonium Glycyrrhizinate and Xiangdan on the serum cholinesterase activity are relatively slow and weak,but the signifiance of those drugs’ effects on the serum cholinesterase activity reminds to further study. [Key words] Chinese medicinal herbal;serum;in vitro;cholinesterase activity 在治疗慢性乙肝的过程中,近年来随着双稠哌啶类生物碱(quinolizidine alkaloids)如苦参碱和氧化苦参碱(苦参素)制剂的广泛应用,临床观察表明在肝功能其他各项指标均有不同程度改善的同时,却可伴有血清胆碱酯酶活性下降[1~6]。另外,皂苷类药物如甘草酸和甘草次酸等保肝药所致的乙酰胆碱酯酶活性抑制亦有报道[7]。因此,我们进行了体外常用几种肝病注射剂血清共孵育实验,检测其对血清胆碱酯酶活性的影响,现将研究结果报告如下。 1 材料与方法 1.1 材料 1.1.1 药物 茵栀黄注射液(10ml/支,江苏常熟制药厂,批号0503151);清开灵注射液(10ml/支,河北神威药业,批号05031312);甘利注射液(10ml/支,连云港正大天晴制药有限公司,批号DG1148);香丹注射液 (10ml/支,杭州正大青春宝制药厂,批号0412281);穿琥宁注射液(50mg/2ml,江西青峰制药有限公司,批号20040808);肝炎灵注射液(2ml/支,其中苦参碱含量不低于35 mg/2ml,江苏常熟制药厂,批号0502021);柴胡注射液(2ml/支,河南援生制药,批号0404131);醒脑静注射液(10ml/支,河南天地药业,批号20050601);鱼腥草注射液(10ml/支,杭州正大青春宝制药厂,批号0502244);葛根素注射液(100mg/2ml,浙江康恩贝制药股份有限公司,批号040502)。 1.1.2 血清 浙江省台州市玉环县中医院检验科收集的血清混合。 1.1.3 试剂及仪器 血清胆碱酯酶活性检测试剂采用北京利德曼公司试剂盒(批号503011)。 1.2 实验方法及结果判断 1.2.1 药物配制 实验药物除阿苦参素粉针剂用200ml注射用水配成浓度为1mg/ml作为高浓度液外,其余各药均以10∶1稀释作为高浓度液。另一实验将上述各高浓度液采用注射用水进行500倍稀释成低浓度液。 1.2.2 检测方法 取各药物的高、低浓度液与等量混合血清混匀,一式3份,将混有药物血清置37℃水浴中孵育10min和24h,以不含药而只加等体积的稀释液为对照,取样采用HITACHI 7080全自动生化分析仪(日立公司产品),按试剂厂家试剂盒说明书设置参数进行胆碱酯酶活性检测。 1.3 统计学方法 用微机全部输入SPSS数据库,计量资料齐性检验后进行方差分析和两两比较和相关性分析。 2 结果 2.1 药物10min作用血清血清胆碱酯酶活性的影响 见表1。

表1 药物短期10min作用血清血清胆碱酯酶活性的影响 (x±s)。

注:*P<0.001,下表均同。

2.2 药物24h作用血清血清胆碱酯酶活性的影响 见表2。

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