新工艺乙醇提取法获取的三藤胶囊混悬液对MRL/lpr狼疮鼠影响的药效学研究

 【摘要】目的 从“量-效”和“时-效”角度,探讨不同浓度三滕胶囊水混悬液对MRL/lpr狼疮鼠的影响。方法 通过新型工艺乙醇提取法获取不同浓度三藤胶囊水混悬液。MRL/lpr狼疮样小鼠48只,随机等分为6组:三藤胶囊水混悬液高、中、低剂量(K、L、M)组、抗狼疮散(Q)组、强的松(R)组和MRL/lpr模型 (S) 组,连续饲养8周,每次灌胃容量0.10 mL/10 g体质量;于给药第0天、4周和8周(结束时),观察小鼠情况并留取小鼠的24 h尿(尿蛋白定量测定,考马斯亮蓝法)、血清(抗ds-DNA抗体水平检测,ELISA方法)和肾脏组织(结束时,PAS染色,半定量分析)。另设8只C57B46小鼠为正常对照组。结果 狼疮鼠给药4周和8周后,体质量变化:K、L和M组的小鼠体质量明显轻于R组(P<0.05);蛋白尿的纠正:L、M、R组的小鼠蛋白尿干预后均有一个下降过程(P<0.05),与S组相比有明显好转(P<0.05);血清抗ds-DNA抗体水平的改善:L、M、Q、R组的小鼠血清抗ds-DNA抗体水平均呈现下降趋势,以L组下降最为明显(P<0.05),且与S组相比有明显下降(P<0.05);肾脏病理变化(总活动指数):K、L、M组小鼠与R组相当,好于S组(P<0.05),肾脏组织PAS染色阳性强度灰阶比值,各干预组均好于模型组(P<0.05)。结论 新工艺乙醇提取法获取的三藤胶囊混悬液各剂量组都能降低MRL/lpr狼疮鼠血清抗ds-DNA抗体的水平,纠正蛋白尿,改善肾脏病理严重度,以中剂量(0.880 g/10 g体质量)的疗效最佳,其作用效价与强的松相当,而无激素样的水钠潴留不良反应;并显示了一定的“量-效”和“时-效”关系。

Pharmacodynamic study of San Teng (ST) extracted by a new method of ethanol extraction on MRL/lpr lupus mice

【Abstract】Objective To investigate the pharmacodynamic function of different concentrations of suspension of “San Teng” (ST) on MRL/lpr lupus mice from the “time-effect” and “quantity-effect′ views. Methods Traditional Chinese herbs of Tripterygium wilfordii Hook f,Sargentodoxa Cuneata (Oliv.) Rehd Et Wils and Spatholobus suberectus Dunn were extracted into different concentrations of ST suspension by a method of Ethanol extraction.Forty eight 20 week old female MRL/lpr lupus mice were randomly divided into six groups,including ST high dose group (K group,1.760 g of crude drug/10 g),ST moderate dose group (L group,0.880 g of crude drug/10 g),ST low dose group (M group,0.440 g of crude drug/10 g),anti-lupus “san” group (Q group,0.022 g pills/10 g),prednisone control group (R group,prednisone 0.125 mg/10 g) and saline control MRL/lpr model group (S group,normal saline) with 8 weeks of continuous feeding.Each mouse was gavaged the capacity of 0.10 mL per 10 g weight body.Normal group was set with eight 8-week-old C57BL/6 female mice for normal saline control.Each 0.30 mL of blood and 24 hours urine were collected on day 0,4 weeks and 8 weeks.The level of serum anti-ds-DNA antibody was detected by ELISA.The protein content of 24 hours urine was detected by method of Coomassie brilliant blue. Results After 4 and 8 weeks intervention of treatment,the body weight in K,L and M groups of mice was significantly lighter than that in R group (P<0.05);The improvement of proteinuria in L,M and R groups was better than that in S group (P<0.05),which showed that the effect of ST suspensions and prednisone could improve the proteinuria in MRL/lpr lupus mice;In improving the level of serum anti-ds-DNA antibody,it was significantly decreased in L,M,Q and R groups comparing with the model S group (P<0.05) especially in L group;On renal pathological changes (total activity index,AI),the AI in K,L and M groups was similar to R group but better than that in group S. Conclusions ST capsule suspension can decrease the levels of serum anti-ds-DNA antibody,correct the proteinuria and ameliorate total activity index of renal pathological changes in MRL/lpr lupus mice.The efficacy was similar to the prednisone,especially in the dose of 0.880 g of crude drug of ST/10 g body weight without the hormone-like side effects of sodium and water retention,and shows a certain “time-effect” and “quantity-effect” relationship.