首页|穿心莲内酯调节NLRP3/caspase-1信号通路对腹泻型肠易激综合征大鼠肠道炎症的影响

穿心莲内酯调节NLRP3/caspase-1信号通路对腹泻型肠易激综合征大鼠肠道炎症的影响

Impact of andrographolide on intestinal inflammation in rats with diarrhea type irritable bowel syndrome by regulating the NLRP3/caspase-1 signaling pathway

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目的 探讨穿心莲内酯(andrographolide,AND)对腹泻型肠易激综合征(irritable bowel syn-drome,IBS-D)大鼠肠道炎症的影响及对NLRP3/caspase-1信号通路的调节机制.方法 利用低浓度乙酸联合束缚应激建立IBS-D大鼠模型后,将大鼠分为对照组、模型组、阳性药物组、AND低剂量(AND-L)组、AND中剂量(AND-M)组、AND高剂量(AND-H)组,每组10只.检测各组大鼠粪便性状评分及粪便含水量;对各组大鼠的腹部收缩反射(abdominal withdrawal reflex,AWR)进行评分;酶联免疫吸附实验(enzyme linked im-munosorbent assay,ELISA)检测各组大鼠结肠组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin 6,IL-6)、白介素-1β(interleukin 1β,IL-Iβ)、白介素-18(interleukin 18,IL-18)水平;Western blot检测各组大鼠结肠组织中NLRP3、ASC、caspase-1蛋白表达水平.结果 对照组大鼠粪便评分为2.43± 0.19、粪便含水量为 31.76±2.81、AWR 评分为 0.43±0.02、TNF-α 为 123.49±12.35、IL-6 为 76.45±6.23、IL-1β 为195.76±15.14、IL-18 为 167.31±13.92,蛋白表达水平 NLRP3 为 0.96±0.06、ASC 为 1.01±0.08、caspase-1 为 0.94± 0.06.模型组大鼠粪便性状评分为6.12±0.58、粪便含水量为65.24±4.13、AWR评分为2.42±0.18,与对照组相比均升高(P<0.05);模型组大鼠 TNF-α 为 315.73±19.47、IL-6 为 231.97±14.65、IL-1β 为 435.83±28.67、IL-18 为382.56±26.84,蛋白表达水平NLRP3 为 2.41±0.18、ASC 为 2.23±0.15、caspase-1 为 2.15±0.16,与对照组相比均升高(P<0.05).AND低、中、高剂量组大鼠的粪便性状评分分别为5.38±0.46、4.57±0.38、3.31±0.27,粪便含水量分别为 54.68±3.67、46.87±3.75、38.11±3.10,AWR 评分分别为 1.79±0.16、1.35±0.10、0.69±0.04,与 模型组相比均降低(P<0.05);AND 低、中、高剂量组大鼠 TNF-α 分别为 268.65±17.23、224.91±16.36、178.16±14.65,IL-6 分别为 187.74±14.57、159.64±11.39、124.18±8.62,IL-1β 分别为 369.51±21.96、314.72±23.64、263.93±16.82,IL-18 分别为 334.72±25.17、280.16±21.43、235.67±19.32,蛋白表达水平 NLRP3 分别为 1.94±0.15、1.56±0.12、1.25±0.09,ASC 分别为 1.89±0.14、1.61±0.13、1.28±0.10,caspase-1 分别为 1.76±0.14、1.49±0.11、1.20±0.09,与模型组相比均降低(P<0.05).结论 AND可能通过抑制NLRP3/caspase-1信号通路减轻IBS-D大鼠的肠道炎症.
Objective To investigate the impact of andrographolide(AND)on intestinal inflammation in rats with diarrhea type irritable bowel syndrome(IBS-D)and its regulatory mechanism on the NLRP3/caspase-1 signaling pathway.Methods After the IBS-D rat model was established by low concentration acetic acid com-bined with restraint stress,the rats were grouped into control group,model group,positive drug group,AND low-dose(AND-L)group,AND medium dose(AND-M)group,and AND high-dose(AND-H)group,with 10 rats in each group.The score of fecal traits and fecal water content of rats in each group were detected;the abdominal with-drawal reflex(AWR)of rats in each group was scored;HE staining was applied to observe the changes of colonic histopathology of rats in each group;enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),and interleukin-18(IL-18)in the colon tissue of rats in each group;Western blot was applied to detect the expression levels of NLRP3,ASC,and caspase-1 proteins in the colon tissue of rats in each group.Results The scores of fecal traits of rats in the control group was 2.43±0.19,fecal water content was 31.76±2.81,AWR score was 0.43±0.02,TNF-α was 123.49±12.35,IL-6 was 76.45±6.23,IL-1β was 195.76±15.14 and IL-18 was 167.31±13.92,the protein expression levels of NL-RP3 was 0.96±0.06,ASC was 1.01±0.08,and caspase-1 was 0.94±0.06.The scores of fecal traits in model group was 6.12±0.58,fecal water content was 65.24±4.13,AWR score was 2.42±0.18,which were higher than those in control group(P<0.05),the TNF-α in model group was 315.73±19.47,IL-6 was 231.97±14.65,IL-1β was 435.83± 28.67,IL-18 was 382.56±26.84,the protein expression levels of NLRP3 was 2.41±0.18,ASC was 2.23±0.15,and caspase-1 was 2.15±0.16,which were higher than those in control group(P<0.05).The scores of fecal traits in the low,medium,and high dose AND groups were 5.38±0.46,4.57±0.38,3.31±0.27,fecal water content were 54.68± 3.67,46.87±3.75,38.11±3.10,AWR scores were 1.79±0.16,1.35±0.10,0.69±0.04,which were higher than those in model group(P<0.05),the TNF-α in the low,medium,and high dose AND groups were 268.65±17.23,224.91± 16.36,178.16±14.65,IL-6 were 187.74±14.57,159.64±11.39,124.18±8.62,IL-1β were 369.51±21.96,314.72± 23.64,263.93±16.82,IL-18 were 334.72±25.17,280.16±21.43,235.67±19.32,the protein expression levels of NL-RP3 were 1.94±0.15,1.56±0.12,1.25±0.09,ASC were 1.89±0.14,1.61±0.13,1.28±0.10,and caspase-1 were 1.76± 0.14,1.49±0.11,1.20±0.09,which were higher than those in model group(P<0.05).Conclusion AND may alle-viate intestinal inflammation in IBS-D rats by inhibiting the NLRP3/caspase-1 signaling pathway.

AndrographolideNOD like receptor protein 3/caspase-1 signaling pathwayDiarrhea type irritable bowel syndromeIntestinal inflammation

郑娟红、庄肇朦、陈怡

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温州市中西医结合医院消化内科,温州 325000

穿心莲内酯 NOD样受体蛋白3/半胱氨酸天冬氨酸蛋白酶1信号通路 腹泻型肠易激综合征 肠道炎症

浙江省医药卫生科技计划项目

2023KY1162

2024

中华内分泌外科杂志
中华医学会

中华内分泌外科杂志

CSTPCD
影响因子:0.657
ISSN:1674-6090
年,卷(期):2024.18(1)
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