摘要
目的 探讨四磨汤对功能性消化不良(FD)大鼠十二指肠微炎症及核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)/胱天蛋白酶1(Caspase-1)/消皮素D(GSDMD)信号通路的影响.方法 用多因素方法建立FD模型.将SD大鼠随机分成正常组、模型组(FD模型)、阳性对照组(灌胃给药0.305 mg·kg-1莫沙必利)和高、中、低剂量实验组(分别灌胃给药5.62、2.81、1.40 g·kg-1四磨汤).测定小肠推进率、胃排空率;用酶联免疫吸附试验法(ELISA)测定血清中白细胞介素(IL)-1β、IL-18水平;用蛋白质印迹法检测十二指肠组织NLRP3、GSDMD的蛋白表达情况.结果 正常组、模型组、阳性对照组和高、中、低剂量实验 组胃排空率 分别为(58.34±5.72)％、(29.16±8.37)％、(48.77±6.10)％、(48.35±6.04)％、(48.20±3.49)％和(39.24±4.20)％;小肠推进率分别为(82.01±7.55)％、(41.95±9.53)％、(64.61±10.18)％、(75.04±9.76)％、(60.58±7.13)％和(45.89±7.40)％;血清 IL-1β 水平分别为(12.86±0.88)、(43.73±4.60)、(18.84±0.86)、(24.61±1.57)、(19.14±0.77)和(29.04±0.72)pg·mL-1;IL-18 水平 分别为(95.00±3.74)、(170.60±8.78)、(108.50±3.05)、(118.90±3.45)、(99.90±8.70)和(141.00±3.71)pg·mL-1;NLRP3 蛋白表达水平分别为 0.32±0.02、0.84±0.05、0.42±0.03、0.48±0.02、0.61±0.04 和 0.62±0.05;GSDMD 蛋白表达水平分别为0.34±0.05、0.93±0.06、0.35±0.03、0.52±0.02、0.53±0.06和0.55±0.05.模型组上述指标与正常组比较,高剂量实验组、阳性对照组上述指标与模型组比较,差异均有统计学意义(P＜0.01或P＜0.05).结论 四磨汤能够有效改善FD大鼠一般状况及十二指肠微炎症,其机制可能与抑制十二指肠NLRP3/Caspase-1/GSDMD信号通路有关.
Abstract
Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.
基金项目
湖南省自然科学基金科卫联合基金(2022JJ70031)
湖南省中医重点专科基金()
湖南省中医药科研计划重点基金(2021203)
湖南中医药大学中医学一流学科开放基金重点项目(4901020000200222)
国家科技期刊平台
NSTL
维普
万方数据