首页|大黄附子汤灌胃对小鼠重症急性胰腺炎的治疗作用及其机制

大黄附子汤灌胃对小鼠重症急性胰腺炎的治疗作用及其机制

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目的 通过建立小鼠重症急性胰腺炎(SAP)模型,观察大黄附子汤对小鼠SAP的治疗作用并分析其机制。方法 SPF小鼠按随机数字表法分为对照组、模型组、大黄附子汤组,每组8只。除对照组外,各组均通过腹腔注射左旋精氨酸建立大鼠SAP模型。大黄附子汤组在建模后6、12 h给予1。5 mL大黄附子汤灌胃,对照组、模型组在同时点给予1。5 mL生理盐水灌胃。末次灌胃结束后麻醉小鼠,采集眼球血,ELISA法检测SAP标志物淀粉酶(AMS)、脂肪酶(LPS)及炎症反应指标肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)。采集小鼠胰腺、肺、结肠组织样本,HE染色进行病理观察,对各组织进行病理学评分。采用免疫组织化学检测及Western blotting检测小肠组织α防御素6(DEFA6)、葡萄糖调节蛋白78(GRP78)蛋白,免疫荧光染色检测小肠组织溶菌酶。结果 血清AMS、LPS、TNF-α、IL-6水平模型组>大黄附子汤组>对照组(P均<0。05)。对照组胰腺、肺、结肠组织结构完整,未见炎症细胞浸润;模型组胰腺、肺、结肠组织结构被破坏,可见红细胞渗出及炎症细胞浸润;大黄附子汤组各组织病理均较模型组有所改善;胰腺、肺、结肠组织病理学评分模型组>大黄附子汤组>对照组(P均<0。05)。小肠组织DEFA6蛋白表达模型组<大黄附子汤组<对照组,GRP78蛋白表达模型组>大黄附子汤组>对照组,溶菌酶相对荧光强度模型组<大黄附子汤组<对照组(P均<0。05)。结论 大黄附子汤灌胃对小鼠SAP具有一定的治疗作用,其机制可能与抑制潘氏细胞内质网应激、增加抗菌分子DEFA6分泌从而改善肠屏障功能有关。
Therapeutic effect and mechanism of Dahuang Fuzi decoction on severe acute pancreatitis in mice
Objective To explore the therapeutic effects of Dahuang Fuzi decoction(DHFZT)on severe acute pan-creatitis(SAP)in mice through the establishment of mouse model with SAP.Methods The SPF mice were randomly di-vided into three groups:control group,model group,and DHFZT group,with 8 mice in each group.Except for the control group,the rat SAP models were established in each group by intraperitoneal injection of L-arginine.Mice in the the DH-FZT group received oral administration of 1.5 mL DHFZT at 6 and 12 h after modeling,while mice in the control and mod-el groups received oral administration of 1.5 mL normal saline.Following the final oral administration,anesthesia was ad-ministered to collect eye samples from all mice for ELISA detection of SAP markers such as amylase(AMS)and lipase(LPS),as well as inflammatory response markers including tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Tissue samples from pancreas,lungs,and colon were collected for histological observation and calculation of histological scores.Immunohistochemistry and Western blotting were used to detect α-defensin 6(DEFA6)protein and glucose regula-tor protein 78(GRP78)in small intestine tissues,respectively;immunofluorescence staining was performed to detect lyso-zyme in the small intestine tissues.Results Serum AMS,LPS,TNF-α,IL-6 level were as follows:model group>DH-FZT group>control group(all P<0.05).In the control group,the tissue structures of pancreas,lung and colon were in-tact,and no inflammatory cell infiltration was observed.In the model group,the tissue structures of pancreas,lung and co-lon were destroyed,and red blood cell exudation and inflammatory cell infiltration were observed.The histopathology of DHFZT group was improved compared with that of the model group.The histopathological scores of pancreas,lung and co-lon were as follows:model group>DHFZT group>control group(all P<0.05).Small intestine DEFA6 protein expression was as follows:model group<DHFZT group<control group,GRP78 protein expression was in the following order:model group>DHFZT group>control group,and the relative fluorescence intensity of lysozyme was as follows:model group<DHFZT group<control group(all P<0.05).Conclusion The intragastric administration of DHFZT exhibits specific therapeutic effects on SAP in mice,potentially by inhibiting endoplasmic reticulum stress in Paneth cells,enhancing the secretion of antibacterial molecules,and thus improving intestinal barrier function.

Dahuang Fuzi decoctionsevere acute pancreatitisPaneth cellsα-defensin 6intestinal barrier functionendoplasmic reticulum stress

孙礼涛、路晓光

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大连大学附属中山医院急诊科,辽宁大连 116001

大黄附子汤 重症急性胰腺炎 潘氏细胞 α防御素 肠屏障功能 内质网应激

国家自然科学基金

81673801

2024

山东医药
山东卫生报刊社

山东医药

CSTPCD
影响因子:1.225
ISSN:1002-266X
年,卷(期):2024.64(17)
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