不同炮制方法对川乌抗痛风性关节炎及心脏毒性作用的影响

Effects of Different Processed Methods on Anti-gouty Arthritis and Cardiotoxicity of Aconiti Radix

目的:研究不同炮制方法对川乌抗痛风性关节炎及心脏毒性的影响,探讨川乌不同炮制方法可能的减毒增效机制。方法:抗痛风性关节炎试验中以大鼠膝关节肿胀度、炎症因子[白细胞介素(IL)-1β,IL-18,肿瘤坏死因子(TNF)-α]水平、肝脏能量代谢相关酶[Ca^(2+)-Mg^(2+)-三磷酸腺苷(ATP)酶,Na^(+)-K^(+)-ATP酶,琥珀酸脱氢酶(SDH)]活性为指标评价2020年版《中华人民共和国药典》收载的方法(简称"药典法")蒸制川乌、药典法煮制川乌、建昌帮法制川乌、樟帮法制川乌及生川乌的抗炎作用。心脏毒性试验中以肌酸激酶(CK),乳酸脱氢酶(LDH)活性和B型脑钠肽(BNP)含量为指标评价川乌及其不同炮制品的心脏毒性强弱。结果:在抗痛风性关节炎试验中,与空白组比较,模型组大鼠膝关节明显肿胀(P<0.01),血清中IL-1β,IL-18,TNF-α水平显著升高(P<0.01),Ca^(2+)-Mg^(2+)-ATP酶活性显著下降(P<0.01)。与模型组比较,生川乌及其炮制品均能减轻大鼠膝关节肿胀,降低血清中IL-1β,IL-18,TNF-α水平;药典法蒸制川乌组大鼠肝脏中Ca^(2+)-Mg^(2+)-ATP酶活性显著高于模型组(P<0.01),其他给药组则均无统计学差异。在心脏毒性试验中,与空白组比较,生川乌组和药典法蒸/煮制川乌组CK,LDH活性显著增强,BNP水平显著上升(P<0.01)。在LDH活性和BNP含量方面,樟帮法和建昌帮法制川乌组显著低于生川乌组(P<0.01);在CK活性方面,樟帮法制川乌组显著低于生川乌组(P<0.01)。结论:生川乌及其炮制品均具有抗炎效果,但在不同评价指标之间存在一定差异;生川乌及其炮制品在心脏毒性方面存在较大差异,其中建昌帮法和樟帮法制川乌的心脏毒性较弱。

Objective:To study the effects of different processing methods on the anti-gouty arthritis and cardiotoxicity of Aconiti Radix,and to explore the possible attenuation and synergism mechanism of these different processing methods.Method:The swelling degree of knee joint,levels of inflammatory factors[interleukin(IL)-1β,IL-18,tumor necrosis factor(TNF)-α]and the activities of liver energy metabolismrelated enzymes[Ca^(2+)-Mg^(2+)-adenosine triphosphatase (ATPase),Na^(+)-K^(+)-ATPase,succinate dehydrogenase(SDH)]in rats with gouty arthritis were used as indicators to evaluate the effects of pharmacopoeia steaming Aconiti Radix,pharmacopoeia boiling Aconiti Radix,Jianchang faction processed Aconiti Radix,Zhang faction processed Aconiti Radix and raw Aconiti Radix.The activity of creatine kinase(CK),lactate dehydrogenase(LDH)and the content of B-type natriuretic peptide(BNP)were used as indexes to evaluate the cardiotoxicity of Aconiti Radix and its different processed products.Result:In the anti-gouty arthritis test,compared with the blank group,the knee joint of the model group was significantly swollen(P<0.01),the levels of IL-1β,IL-18,and TNF-αin serum were significantly increased(P<0.01),and the Ca^(2+)-Mg^(2+)-ATPase activity was significantly decreased(P<0.01).Compared with the model group,raw Aconiti Radix and the four processed products could reduce knee joint swelling and decrease IL-1β,IL-18,and TNF-αlevels in serum of rats.The activity of Ca^(2+)-Mg^(2+)-ATPase in the liver of rats from the pharmacopoeia steaming Aconiti Radix group was significantly higher than that in the model group (P<0.01),and there was no statistical difference in other groups.In the cardiotoxicity test,compared with the blank group,the activities of CK and LDH were significantly increased and the level of BNP was significantly increased in the raw Aconiti Radix group and the pharmacopoeia steaming/boiling Aconiti Radix groups(P<0.01).In terms of LDH activity and BNP content,the Zhang faction and Jianchang faction processed Aconiti Radix groups were significantly lower than those in the raw Aconiti Radix group(P<0.01).In the CK activity,the Zhang faction processed Aconiti Radix group was significantly lower than that in the raw Aconiti Radix group(P<0.01).Conclusion:Raw Aconiti Radix and the four processed products have certain anti-inflammatory effects,but there are some differences among different indicators.There are significant differences in cardiotoxicity between the raw products and processed products of Aconiti Radix,and the cardiotoxicity of Jianchang faction and Zhang faction processed products was the weakest.