不同剂型的砂生槐总生物碱对多房棘球蚴小鼠的药效学作用  

Pharmacodynamic effects of different formulations of total alkaloids of Sophora moocrorftiana on Echinococcus multilocularis in mice

作　　者：甘雪辉 胡春晖 都涛 高瑞雪 高攀[3] 张发斌[1] GAN Xuehui;HU Chunhui;DU Tao;GAO Ruixue;GAO Pan;ZHANG Fabin(Qinghai University,Xining 810001,China;General Hospital of the Western Theater Command,Chengdu 610083,China;Shaanxi University of Chinese Medicine,Xianyang 712046,China)

机构地区：[1]青海大学,青海西宁810001 [2]西部战区总医院,四川成都610083 [3]陕西中医药大学,陕西咸阳712046

出　　处：《中国高原医学与生物学杂志》2022年第1期51-58,共8页Journal of Chinese High Altitude Medicine & Biology

基　　金：国家自然科学基金项目(81960641);青海大学青年基金现目团队项目(2020-QYY-1)。

摘　　要：目的探讨不同剂型的砂生槐总生物碱对多房棘球蚴小鼠的药效学作用。方法通过腹腔注射多房棘球蚴原头节完成小鼠造模4个月后,将经多普勒超声检测造模成功的小鼠随机分为片剂组、水剂组,于给药15,30,60天时,计算囊重指数、脾脏指数;采用流式细胞技术检测脾脏组织中的CD_(4)^(+)、CD_(8)^(+)T,B细胞相对含量;采用实时荧光定量PCR技术(q-PCR)检测肝脏组织中转化生长因子-β(TGF-β1基因)、细胞周期关键调控因子Gadd45γ(Gadd45γ基因)的mRNA相对表达量;采用试剂盒检测碱性磷酸酶、γ-谷氨酰转肽酶sCaspase 3活性;采用HE染色法观察肝脏微观结构变化。满足正态分布的计量资料采用均数±标准差表示,组间比较采用t检验和单因素方差分析。结果予片剂和水剂砂生槐总生物碱15天,囊重指数无统计学差异(P>0.05),30、60天片剂组明显低于水剂组(t=3.578,t=3.883;P<0.01,P<0.01);予片剂和水剂砂生槐总生物碱15.30,60天,片剂组脾脏指数明显高于水剂组(t=2.939,t=6.859,t=3.674;P<0.05,P<0.01,P<0.01);脾脏组织中的CD_(4)^(+)/CD_(8)^(+)差异有统计学意义,30,60天时片剂组高于水剂组(t=3.925,t=5.203;P<0.01,P<0.01);治疗15,30,60天时TGF-β1的相对表达量片剂组明显低于水剂组(t=2.969,t=2.706,t=2.738;P<0.05,P<0.05,P<0.05);砂生槐总生物碱治疗30天,肝脏组织中Gadd45γ的相对表达量片剂组低于水剂组(t=2.652;P<0.05)。治疗15,30,60天时碱性磷酸酶水平有统计学意义,片剂组明显低于水剂组(t=2.378,t=5.435,t=4.382;P<0.05,P<0.01,P<0.01);不同剂型的砂生槐总生物碱治疗15,30,60天时,T/B比例和γ-谷氨酰转肽酶.Caspase 3活性值无统计学差异(P>0.05)。HE染色结果显示:水剂组小鼠肝组织中出现炎症因子浸润,片剂组接近正常。结论砂生槐总生物碱片剂和水剂对多房棘球蚴病小鼠治疗有效,且片剂药效更佳。Objective To explore the pharmacodynamic effects of different formulations of total alkaloids of So-phora moocroiftiana(TA-SM)on Echinococcus multilocularis in mice.Methods Four months after the completion of mouse modeling by intraperitoneal injection of Echinococcus multilocularis protocephalus,the mice that were successfully modeled by Doppler ultrasound were randomly divided into tablet group and liquid group.The sac weight index and spleen index were calculated at 15 d,30 d and 60 d of administration.CD_(4)^(+),CD_(8)^(+),T cells and B cells in spleen tissue were detected by flow cytometry;Real-time fluorescent quantitative PCR technology(q-PCR)was used to detect the relative expression of transforming growth factor-β(TGF-β gene)and the key cell cycle regulator Gadd45γ(Gadd45γgene)in liver tissue;Alkaline phosphatase,7-glutamyl transpeptidase and Caspase 3 activity were detected by relative kits.HE staining method was used to observe the changes in liver microstructure.The measurement data that satisfies the normal distribution were represented by x±s,and the difference between groups was compared by t-test and ANOVA.Results There was no significant difference in sac weight index between tablet and liquid groups for 15 days(P>0.05),while the index of tablet group was significantly lower than that of liquid group for 30 and 60 days(t=3.578,t=3.883;P<0.01,P<0.01);the spleen index of tablet group was significantly higher than that of liquid group(t=2.939,t=6.859,t=3.674;P<0.05,P<0.01,P<0.01)after given the tablet and liquid groups of TA-SM for 15,30,and 60 days;the difference of CD_(4)^(+)/CD_(8)^(+)in spleen tissue was statistically significant,and the tablet group was higher than liquid group at 30 and 60 days(t=3.925,t=5.203;P<0.01,P<0.01);the relative expression of TGF-β1 at 15,30,and 60 days of treatment in the tablet group was significantly lower than that in the liquid group(t=2.969,t=2.706,t=2.738;P<0.05,P<0.05,P<0.05);after 30d of TA-SM treatment,the relative expression of Gadd45-y in the liver t

关 键 词：砂生槐总生物碱 片剂 水剂 多房棘球蚴病 药效学 

分 类 号：R978[医药卫生—药品]