香砂六君子对脾胃虚弱型功能性消化不良大鼠十二指肠低度炎症的作用研究

Study of Xiangsha Liujunzi on low-grade duodenal inflammation in rats with functional dyspepsia of spleen stomach weakness

目的基于Nod结构域样受体3(NLRP3)活化探讨香砂六君子(XSLJZ)对脾胃虚弱型功能性消化不良(FD)大鼠十二指肠低度炎症的干预效应及机制。方法将SD大鼠随机分为空白组与造模组,通过复合造模法(碘乙酰胺灌胃+游泳力竭+饥饱失常)建立脾胃虚弱型FD大鼠,并进行模型验证。将成功建模的脾胃虚弱型FD大鼠随机分为模型组和低(6 g·kg^(-1))、高(12 g·kg^(-1))剂量实验组。给药2周后,检测各组大鼠体质量及进食量并测算其胃排空率及肠推进率,以酶联免疫吸附试验法测定各组大鼠血清中白细胞介素(IL)-1β、IL-18的含量,以蛋白质印迹法及免疫荧光染色(IF)法检测NLRP3、胱天蛋白酶-1(caspase-1)、孔蛋白Gasdermoh-D(GSDMD)蛋白的表达水平。结果给药后,空白组、模型组和低、高剂量实验组的体质量分别为(390.50±34.30)、(305.20±33.10)、(338.30±34.84)和(352.40±33.40)g,3 h进食量分别为(14.51±1.36)、(10.31±1.37)、(12.99±1.34)和(13.77±1.55)g,胃排空率分别为(56.75±5.05)%、(29.50±5.02)%、(46.40±6.83)%和(47.30±9.00)%,肠推进率分别为(86.66±12.26)%、(35.38±11.53)%、(60.29±13.26)%和(75.09±10.10)%,IL-1β含量分别为(29.27±4.79)、(47.18±8.98)、(38.04±2.92)和(31.22±4.97)pg·mL^(-1),IL-18含量分别为(23.12±5.47)、(110.62±18.33)、(72.99±8.40)和(40.36±6.83)ng·mL^(-1);模型组的上述指标与空白组和低、高剂量实验组比较,差异均有统计学意义(P<0.05,P<0.01)。结论XSLJZ可以有效抑制十二指肠低度炎症,其机制可能与NLRP3活化有关。

Objective To investigate the effect and molecular mechanism of Xiangsha Liujunzi(XSLJZ)on low-grade duodenal inflammation in rats with functional dyspepsia(FD)of spleen-stomach weakness based on Nod domain-like receptor 3(NLRP3)activation.Methods SD rats were randomly divided into blank group and model group.FD rats with weakness of spleen and stomach were reconstructed by compound modeling method(iodoacetamide gavage+swimming exhaustion+hunger-satiety disorder),and the model was verified.FD rats with spleen and stomach weakness were randomly divided into model group and low(6 g·kg^(-1)),high(12 g·kg^(-1))experimental dose groups.After 2 weeks of administration,the body weight and food intake of rats in each group were measured and their gastric emptying rate and intestinal propulsion rate were measured.The contents of IL-1βand IL-18 in the serum of rats in each group were determined by enzyme-linked immunosorbent assay(ELISA).The expression levels of NLRP3,caspase-1 and GSDMD protein were detected by Western blot(WB)and immunofluorescence staining(IF).Results The body weight of blank group,model group and low,high dose experimental groups were(390.50±34.30),(305.20±33.10)(338.30±34.84)and(352.40±33.40)g;the 3-hour food intake were(14.51±1.36),(10.31±1.37),(12.99±1.34)and(13.77±1.55)g;the gastric emptying rate were(56.75±5.05)%,(29.50±5.02)%,(46.40±6.83)%and(47.30±9.00)%;the intestinal propulsion rate were(86.66±12.26)%,(35.38±11.53)%,(60.29±13.26)%and(75.09±10.10)%;IL-1βcontents were(29.27±4.79),(47.18±8.98),(38.04±2.92)and(31.22±4.97)pg·mL^(-1);IL-18 contents were(23.12±5.47),(110.62±18.33),(72.99±8.40)and(40.36±6.83)pg·mL^(-1).The above indexes of model group were statistically significant compared with blank group and low,high-dose experimental groups(P<0.05,P<0.01).Conclusion XSLJZ can effectively inhibit low-grade duodenal inflammation,and the mechanism may be related to NLRP3 activation.