[1]代晓玉,吴秋葶,姚佳琦,等.升降散治疗急性胰腺炎并发多器官功能障碍机制研究[J].陕西中医杂志,2022,(5):550-554.[doi:DOI:10.3969/j.issn.1000-7369.2022.05.002]
　DAI Xiaoyu,WU Qiuting,YAO Jiaqi,et al.The potential mechanisms of Shengjiang powder protect against multiple organ dysfunction in acute pancreatitis mice[J].,2022,(5):550-554.[doi:DOI:10.3969/j.issn.1000-7369.2022.05.002]
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升降散治疗急性胰腺炎并发多器官功能障碍机制研究
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《陕西中医》杂志[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2022年5期
页码:
550-554
栏目:
基础研究
出版日期:
2022-05-05

文章信息/Info

Title:
The potential mechanisms of Shengjiang powder protect against multiple organ dysfunction in acute pancreatitis mice
作者:
代晓玉; 吴秋葶; 姚佳琦; 李 娟; 万美华; 唐文富
(四川大学华西医院,四川 成都 610041)
Author(s):
DAI Xiaoyu; WU Qiuting; YAO Jiaqi; LI Juan; WAN Meihua; TANG Wenfu
(West China Hospital,Sichuan University,Chengdu 610041,China)
关键词:
急性胰腺炎;  多器官功能障碍;  升降散;  色氨酸代谢;  色氨酸-犬尿氨酸代谢通路;  炎症调节
Keywords:
Acute pancreatitis;  Multiple organ dysfunction syndromes;  Shengjiang powder;  Tryptophan metabolism;  Tryptophan-kynurenine pathway;  Inflammatory regulation
分类号:
R 657.51
DOI:
DOI:10.3969/j.issn.1000-7369.2022.05.002
文献标志码:
A
摘要:
目的:分析升降散对急性胰腺炎(AP)的治疗效果及其潜在的作用机制和靶点。方法:将24只雄性C57小鼠随机分为假手术组、模型组、治疗组与对照组。采用雨蛙素及脂多糖联合腹腔注射构建AP并发多器官功能障碍(MODS)模型。造模2 h后,假手术组和模型组均用0.9%氯化钠溶液按5 g/kg剂量灌胃,治疗组按5 g/kg剂量灌胃给药升降散,对照组按30 mg/kg剂量腹腔注射给药犬尿氨酸-3-单加氧酶(KMO)抑制剂GSK180。比较各组间小鼠血清淀粉酶、脂肪酶水平,色氨酸-犬尿氨酸通路的代谢产物水平及多个器官病理评分。结果:模型组小鼠的血清淀粉酶、脂肪酶水平较假手术组显著升高(P<0.05),而升降散和GSK180均显著降低淀粉酶、脂肪酶水平,且两者比较差异有统计学意义(P<0.05)。模型组多个器官病理评分较假手术组显著升高(均P<0.05); GSK180显著下调胰腺、肺脏、心脏、肝脏、肾脏病理评分(均P<0.05); 升降散显著下调胰腺、肺脏、肾脏、结肠病理评分(P<0.05)。模型组小鼠血清中色氨酸-犬尿氨酸通路的关键代谢产物较假手术组明显改变(均P<0.05),如促炎产物犬尿氨酸(KYN)、3-羟基犬尿氨酸(3-HK)明显上升,抗炎产物犬尿喹啉酸(KYNA)明显下调。GSK180可显著下调KYN、3-HK。升降散可显著下调3-HK,上调KYNA(P<0.05)。结论:升降散对急性胰腺炎并发多器官障碍具有显著的保护作用,其机制可能与调节色氨酸-犬尿氨酸代谢通路,抑制KMO活性密切相关。
Abstract:
Objective:This study aimed to explore the potential effect and underlying mechanism of Shengjiang powder(SJP),a classical Chinese formula,on mice with acute pancreatitis(AP).Methods:Twenty-four male C57 mice were randomly divided into the regular group with sham operation(SOG),AP model group(MG),treatment group(TG),and control group(CG).The model of AP-MODS was induced by intraperitoneal injection of caerulein and lipopolysaccharide.After 2 hours of molding,the SOG and MG were treated with saline(5 g/kg),and the TG was treated with SJP(5 g/kg)by gavage.The CG was treated by the inhibitor of kynurenine 3-monooxygenase(KMO)GSK180,through abdominal injection at 30 mg/kg.The levels of serum amylase,lipase,and crucial metabolites in the tryptophan-kynurenine(TRP-KYN)pathway; and the pathological scores of multiple organs were compared across groups.Results:The AP-MODS mice model found an apparent increase of amylase and lipase(P<0.05).SJP and GSK180 both decreased amylase and lipase(P<0.05), and there was statistically significant difference between them.Multiple organs severe pathological injuries were observed in the AP model(all P<0.05), but GSK180 decreased the pathological scores of the pancreas, lung, heart, liver, and kidney significantly(all P<0.05).Also, SJP decreased the scores of the pancreas, lung, kidney, and colon profoundly(all P<0.05).The crucial metabolites concentration of the TRP-KYN pathway were obviously disturbed by AP-MODS(all P<0.05).Notably, pro-inflammatory metabolites like KYN and 3-hydroxy-kynurenine(3-HK)increased, and anti-inflammatory metabolites, kynurenic acid(KYNA)decreased.GSK180 reduced KYN(P<0.05)and 3-HK(P<0.05)significantly.Similarly, SJP reduced 3-HK but raised KYNA(P<0.05).Conclusion:SJP has a significant protective effect on AP-MODS,the mechanism of which may be closely related to regulating the TRP-KYN pathway and inhibiting KMO activity.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81603519)
更新日期/Last Update: 2022-05-09