甘遂半夏汤中甘遂甘草反药组合加减应用对腹水大鼠利水及免疫方面的影响

Effects of application of modified Gansui and Gancao anti-drug combination in Gansui Banxia Decoction on diuretic effect and immunity in malignant ascites rat

目的:从利水及免疫两个方面探讨甘遂半夏汤药效的产生是否与甘遂甘草反药组合相关。方法:将153只Wistar大鼠按体质量随机区组设计分为正常组、模型组、呋塞米组、甘遂半夏汤全方组、甘遂半夏汤去醋甘遂组、甘遂半夏汤去炙甘草组、甘遂半夏汤去炙甘草醋甘遂组,腹腔注射Walker-256细胞复制大鼠腹水模型,正常组和模型组灌胃蒸馏水,其余各组灌胃相应药物。给药9d后,取材前后称量大鼠体质量,测量腹水量,放完腹水后腹主动脉取血,检测PRL1、AⅡ、ALD、ADH。取材前抽取大鼠腹水10 mL,检测腹水中IL-2、IL-6、TNF-α、IFN-γ和VEGF含量。结果:与正常组比较,模型组大鼠体质量在给药第1、4、8天均显著降低(P<0.01),大鼠腹围/体质量比值、ALD、ADH含量均显著升高(P<0.01,P<0.05),净体质量、尿量均显著降低(P<0.01)。与模型组比较,给药第4天各给药组大鼠体质量均升高(P<0.05,P<0.01),给药第1、4天,甘遂半夏汤组大鼠腹围/体质量比值降低(P<0.05,P<0.01),尿量升高(P<0.05),腹水量降低(P<0.01),血中ADH含量降低(P<0.05),腹水中IL-6和VEGF含量降低(P<0.05),IFN-γ含量升高(P<0.05)。与甘遂半夏汤组比较,甘遂半夏汤去炙甘草组大鼠血中ALD含量升高(P<0.05),甘遂半夏汤去醋甘遂组大鼠血中ADH和腹水中IL-6含量升高(P<0.05),腹水中IFN-γ含量降低(P<0.05),甘遂半夏汤去炙甘草醋甘遂组大鼠腹水量增加(P<0.05),腹水中IL-6、VEGF含量升高(P<0.01,P<0.05)。结论:各给药组在改善腹水模型大鼠利水作用相关指标方面均未表现出明显的毒性,且甘遂半夏汤组在改善利水相关指标方面的作用优于甘遂半夏汤去掉其中一味反药或两味反药组,其发挥利水的机制可能与其抑制肾素-血管紧张素-醛固酮-抗利尿激素系统,促进尿液排泄,同时与甘遂半夏汤具有一定调节IL-6、IFN-γ、VEGF等细胞因子,进而杀伤Walker-256细胞,减少腹水的生成有关。

Objective:To discuss whether the efficacy of Gansui Banxia Decoction is related to the anti-drug combination of Gansui and Gancao from the aspects of promoting water and immunity.Methods:A total of 153 male Wistar rats were randomly divided into a normal group,model group,furosemide group,Gansui Banxia Decoction group,Gansui Banxia Decoction Removed Zhigancao group,Gansui Banxia Decoction removed Cugansui group,Gansui Banxia Decoction removed Zhigancao and Cugansui group.Rats were injected with Walker-256 cells in enterocoelia to replicate the ascites model.The normal group and model group were given distilled water by gavage,and the other groups were given drugs by gavage.Administered nine days,when we remove the ascites,we also need to weigh the body weight and ascites volume of rats before and after obtaining materials.When we remove the ascites,we need to abdominal aortic blood,centrifuge testing renin(PRL1),angiotensinⅡ(AⅡ),aldosterone(ALD),antidiuretic hormone(ADH).Before anesthetic injection,10 mL of ascites were taken from rats to detect the contents of IL-2,IL-6,TNF-α,IFN-γand VEGF.Results:Compared to the normal group,the weight of the model group was decreased on the first,forth,eighth day of administration(P<0.01),the abdominal girth/body weight ratio,the content of ALD and AVP were increased(P<0.01,P<0.05),the net weight,the urine of rats in the model group was lower(P<0.01).Compared with the model group,the weight of the treatment groups was statistically increased on the forth day of administration(P<0.05,P<0.01);the abdominal girth/body weight ratio of rats in the groups of Gansui Banxia Decoction was lower than the model group on the frst and the forth day of administration(P<0.05,P<0.01),the urine in the groups of Gansui Banxia Decoction was higher(P<0.05),but the ascites was lower(P<0.01),the amount of ADH,the content of IL-6 and VEGF in the groups of Gansui Banxia Decoction was decresed(P<0.05),but the content of IFN-γwas significantly increased(P<0.05).Compared whith the Gansui Banxia Decoction group,the ALD in the group of Gansui Banxia Decoction removed Zhigancao was rised(P<0.05),the ADH and IL-6 in the groups of Gansui Banxia Decoction removed Cugansui was rised(P<0.05),but the content of IFN-γwas decreased(P<0.05);the ascites,the content of IL-6 and VEGF in the ascites of the Gansui Banxia Decoction removed Zhigancao and Cugansui was rised(P<0.01,P<0.05).Conclusion:None of the treatment groups show significant toxicity in improving the water-related indexes of ascites model rats,and the effect of the Gansui Banxia Decoction group in improving water-related indexes is better than the group of Gansui Banxia Decoction remove Zhigancao or Cugansui or Zhigancao and Cugansui.The mechanism of drug Gansui Banxia Decoction’s beneficial effect on water may be related to its inhibition of renin-angiotensin-aldosterone-antidiuretic hormone system and its promotion of urine excretion.Meanwhile,Gansui Banxia Decoction has certain regulation of cytokines such as IL-6,IFN-γand VEGF,thus killing Walker-256 cells and reducing the formation of ascites.