Intervention effect of Dahuang Mudan Decoction plus Sijunzi Decoction on DBTC induced pancreatic fibrosis in rats

JI Xiaodan; LI Xingjia; LYU Chan; HAO Lixiao; LI Tao; GONG Biao

doi:10.16305/j.1007-1334.2022.2204074

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Intervention effect of Dahuang Mudan Decoction plus Sijunzi Decoction on DBTC induced pancreatic fibrosis in rats

更新时间：2022-10-26

- Intervention effect of Dahuang Mudan Decoction plus Sijunzi Decoction on DBTC induced pancreatic fibrosis in rats
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 10, Pages: 45-52(2022)
- 作者机构：
  
  1.上海中医药大学附属曙光医院消化科（上海 201203）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2204074
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纪晓丹,李兴佳,吕婵,等.大黄牡丹汤合四君子汤对DBTC诱导大鼠胰腺纤维化的干预作用[J].上海中医药杂志,2022,56(10):45-52.

JI Xiaodan,LI Xingjia,LYU Chan,et al.Intervention effect of Dahuang Mudan Decoction plus Sijunzi Decoction on DBTC induced pancreatic fibrosis in rats[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(10):45-52.
纪晓丹,李兴佳,吕婵,等.大黄牡丹汤合四君子汤对DBTC诱导大鼠胰腺纤维化的干预作用[J].上海中医药杂志,2022,56(10):45-52. DOI： 10.16305/j.1007-1334.2022.2204074.

JI Xiaodan,LI Xingjia,LYU Chan,et al.Intervention effect of Dahuang Mudan Decoction plus Sijunzi Decoction on DBTC induced pancreatic fibrosis in rats[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(10):45-52. DOI： 10.16305/j.1007-1334.2022.2204074.

摘要

目的,2,研究大黄牡丹汤合四君子汤对二丁基二氯化锡（DBTC）诱导大鼠胰腺纤维化的干预作用。,方法,2,48只雄性SD大鼠随机分成正常组、模型组、大黄牡丹汤组、四君子汤组、大黄牡丹汤合四君子汤合方组（简称“合方组”）、对照组，每组8只。正常组尾静脉注射质量分数为0.9%的氯化钠溶液（1 mL/kg），其他组尾静脉注射DBTC（8 mg/kg）造模。造模第2天开始每天按每100 g大鼠体质量1 mL灌胃相应药物，连续3周。其中大黄牡丹汤组给予大黄牡丹汤（生药含量0.63 g/mL），四君子汤组给予四君子汤（生药含量0.24 g/mL），合方组给予大黄牡丹汤合四君子汤（生药含量0.87 g/mL），对照组给予辅酶Q10（5 mg/kg），正常组和模型组灌胃等体积质量分数为0.9%的氯化钠溶液。末次给药后，收集大鼠胰腺组织，分离血清。检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、白蛋白（ALB）、总胆汁酸（TBA）、肌酐（Cr）、尿素（UREA）、白介素-6（IL-6）含量。采用HE染色、天狼猩红染色观察胰腺组织形态学改变，免疫组化法观察Ⅰ型胶原蛋白α1（COLⅠA1）、α-平滑肌肌动蛋白（α-SMA）表达。,结果,2,与正常组比较，模型组大鼠ALT、AST活性均显著升高（,P,<,0.05）；HE染色显示，模型组大鼠胰腺呈萎缩状，胰腺导管和腺泡结构破坏，纤维组织增生，部分小叶间构成一片红染的无结构区，胰腺间质可见大量炎细胞浸润；天狼猩红染色显示，模型组大鼠胰腺组织中部分破坏和萎缩的腺泡结构被胶原纤维替代，破坏的腺泡、小叶和胰岛呈结节状纤维化；且天狼猩红阳性染色面积比（SR）也显著增加（,P,<,0.05）。与模型组相比，各药物干预组大鼠ALT、AST活性均有不同程度降低（,P<,0.05）；各药物干预组大鼠胰腺组织SR亦有不同程度降低（,P,<,0.05）；各药物干预组大鼠胰腺组织的COLⅠA1以及α-SMA蛋白的表达组间差异具有统计学意义（,P,<,0.05）。与大黄牡丹汤组及四君子汤组相比，合方组ALT、AST活性均有降低（,P,<,0.05）；与合方组比较，大黄牡丹汤组、四君子汤组、对照组α-SMA、COLⅠA1蛋白的表达差异均有统计学意义（,P,<,0.05）。,结论,2,大黄牡丹汤合四君子汤可显著改善DBTC诱导大鼠胰腺纤维化，且存在一定程度的配伍增效作用。

Abstract

Objective,2,To study the intervention effect of Dahuang Mudan Decoction plus Sijunzi Decoction on pancreatic fibrosis induced by dibutyltin dichloride （DBTC） in rats.,Methods,2,Forty-eight male SD rats were randomly divided into a blank group， a DBTC model group， a Dahuang Mudan Decoction group， a Sijunzi Decoction group， a Dahuang Mudan Decoction plus Sijunzi Decoction group （referred to as “compound group”） and a coenzyme Q10 control group， with 8 rats in each group. The blank group was administered with caudal vein injection of normal saline （1 mL/kg）， other groups were injected with DBTC （8 mg/kg） intravenously in the tail vein. Starting from the second day of molding， the corresponding drugs administered by gavage at 1 mL per 100 g of rat body mass every day for 3 weeks. The rats in the Dahuang Mudan Decoction group were given Dahuang Mudan Decoction （raw drug content 0.63 g/mL）， those in the Sijunzi Decoction group were given Sijunzi Decoction （raw drug content 0.24 g/mL）， those in the compound group were given Dahuang Mudan Decoction plus Sijunzi Decoction （raw drug content 0.87 g/mL）， those in the control group were given Coenzyme Q10 （5 mg/kg）， and those in the blank and model groups were given equal volume of 0.9% NaCl solution by gavage. After the final administration， pancreatic tissues of rats were collected and serum was isolated. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， albumin （ALB）， total bile acid （TBA）， creatinine （Cr）， urea （UREA） and interleukin-6 （IL-6） contents were detected. HE staining and Sirius scarlet staining were used to assess the pancreatic histological morphology， and immunohistochemistry were used to investigate the expression of type I collagen α1 （COLⅠA1） and α-smooth muscle actin （α-SMA）.,Results,2,Compared with the blank group， the activities of ALT and AST in the DBTC model group were significantly increased （,P,<,0.05）. HE staining showed that the pancreatic glands in the DBTC model group were atrophic， with destruction of pancreatic ducts and acinar vesicles， fibrous tissue hyperplasia， a red-stained structureless area between some lobules， and a large number of inflammatory cells infiltrated in the pancreatic interstitium. Sirius scarlet staining showed that some of the destroyed and atrophied acinar structures in the pancreatic tissue of rats in the DBTC model group were replaced by collagen fibers， and the damaged acini， lobules and islets presented nodular fibrosis. The surface ratio （SR） of positive Sirius scarlet staining also increased significantly （,P,<,0.05）. Compared with the model group， the ALT and AST activities of rats in each drug intervention group decreased to different degrees （,P,<,0.05）； the SR of pancreatic tissue in each drug intervention group also decreased to different degrees （,P,<,0.05）； and the differences in the expression of COLⅠA1 and α-SMA protein in pancreatic tissues of rats in each drug intervention group were statistically significant （,P,<,0.05）. Compared with Dahuang Mudan Decoction group and Sijunzi Decoction group， the activities of ALT and AST in the compound group decreased （,P,<,0.05）. Compared with the compound group，the differences in the expression of COLⅠA1 and α-SMA proteins in pancreatic tissues of rats in the Dahuang Mudan Decoction group， Sijunzi Decoction group and coenzyme Q10 group were statistically significant （,P,<,0.05）.,Conclusion,2,Dahuang Mudan Decoction plus Sijunzi Decoction can significantly improve DBTC induced pancreatic fibrosis in rats， and there is a certain degree of effect-enhancing mechanism through compatibility.

关键词

慢性胰腺炎胰腺纤维化大黄牡丹汤四君子汤复方配伍大鼠模型中药研究

Keywords

chronic pancreatitispancreatic fibrosisDahuang Mudan DecoctionSijunzi Decoctioncompatibility of compound formularat modeltraditional Chinese herbal medicine research

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