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基于PI3K/AKT信号通路的大黄牡丹汤对急性胰腺炎大鼠肺组织细胞凋亡及炎症反应的影响     被引量:23

Effects of Dahuang Mudan Decoction on Apoptosis and Inflammatory Reaction in Lung Tissue of Rats with Acute Pancreatitis Based on PI3K/AKT Signaling Pathway

文献类型:期刊文献

中文题名:基于PI3K/AKT信号通路的大黄牡丹汤对急性胰腺炎大鼠肺组织细胞凋亡及炎症反应的影响

英文题名:Effects of Dahuang Mudan Decoction on Apoptosis and Inflammatory Reaction in Lung Tissue of Rats with Acute Pancreatitis Based on PI3K/AKT Signaling Pathway

作者:杨丹[1,2];孙银凤[1];白敏[1];宋冰[1,2];张延英[1,2];汪永锋[1,2];康万荣[1,2]

第一作者:杨丹

机构:[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃省实验动物行业技术中心,甘肃兰州730000

第一机构:甘肃中医药大学

年份:2022

卷号:29

期号:7

起止页码:73

中文期刊名:中国中医药信息杂志

外文期刊名:Chinese Journal of Information on Traditional Chinese Medicine

收录:CSTPCD;;CSCD:【CSCD_E2021_2022】;

基金:国家自然科学基金(82160871、81760828);甘肃省自然科学基金(20JR5RA186);甘肃中医药大学科学研究与创新基金(2021KCYB-6)。

语种:中文

中文关键词:急性胰腺炎;大黄牡丹汤;肺损伤;炎症反应;凋亡;PI3K/AKT信号通路;大鼠

外文关键词:acute pancreatitis;Dahuang Mudan Decoction;lung injury;inflammatoryreaction;apoptosis;PI3K/AKT signalingpathway;rats

摘要:目的观察大黄牡丹汤对急性胰腺炎大鼠肺组织细胞凋亡及炎症反应的影响,基于PI3K/AKT信号通路探讨其作用机制。方法96只SPF级Wistar大鼠随机分为空白组、模型组、奥曲肽组和大黄牡丹汤高、中、低剂量组,每组16只。除空白组外,其余各组采用经胰胆管逆行注射5%牛磺胆酸钠溶液造模。各组造模前1 h及造模后12、24 h各给药1次,奥曲肽组予0.01 mg/kg奥曲肽皮下注射,大黄牡丹汤高、中、低剂量组分别予14、7、3.5 g/kg大黄牡丹汤灌胃,空白组和模型组予等体积蒸馏水灌胃。观察大鼠一般状态;生化分析仪测定大鼠血清淀粉酶(AMS)、C反应蛋白(CRP)含量;HE染色观察胰腺和肺组织病理变化;ELISA检测肺组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6含量;RT-PCR检测肺组织PI3K、AKT、Caspase-3、Bcl-2、Bax mRNA表达;Westernblot检测肺组织PI3K、p-AKT、Caspase-3、Bcl-2、Bax蛋白表达。结果与空白组比较,模型组大鼠一般生存状态不佳,血清AMS、CRP含量显著增加(P<0.01),HE染色可见胰腺、肺组织坏死、充血、结构不完整,肺组织TNF-α、IL-1β、IL-6含量显著增加(P<0.01),PI3K、Caspase-3、Bax mRNA和蛋白表达显著升高,Bcl-2 mRNA和蛋白表达显著降低,AKT mRNA和p-AKT蛋白表达显著升高(P<0.01);与模型组比较,各给药组大鼠一般生存状态有不同程度改善,血清AMS、CRP含量有不同程度降低,胰腺、肺组织水肿、坏死程度明显改善,奥曲肽组和大黄牡丹汤高、中剂量组大鼠肺组织TNF-α、IL-1β、IL-6含量显著减少(P<0.01,P<0.05),奥曲肽组和大黄牡丹汤高剂量组大鼠肺组织PI3K、Caspase-3、Bax mRNA和蛋白表达显著降低,Bcl-2 mRNA和蛋白表达显著升高,AKT mRNA和p-AKT蛋白表达显著降低(P<0.01,P<0.05)。结论大黄牡丹汤对急性胰腺炎大鼠有较好改善作用,其作用机制可能与抑制PI3K/AKT信号通路,减轻肺组织病理损伤,抑制细胞凋亡及炎症反应有关。
Objective To observe the effects of Dahuang Mudan Decoction on apoptosis and inflammatory reaction in lung tissue of rats with acute pancreatitis;To study its mechansim based on PI3K/AKT signaling pathway.Methods Totally 96 SPF Wistar rats were randomly divided into blank group,model group,octreotide group and Dahuang Mudan Decoction high-,medium-and low-dosage groups,with 16 rats in each group.Except for the blank group,the other groups were made by retrograde injection of 5%sodium taurocholate solution through pancreaticobiliary duct.Each group was dosed 1 hour before modeling,12 hours and 24 hours after modeling.The octreotide group was given subcutaneous injection of 0.01 mg/kg octreotide,Dahuang Mudan Decoction high,medium-,and low-dosage groups were given 14,7,and 3.5 g/kg Dahuang Mudan Decoction by gavage respectively,and the blank group and model group were given an equal volume of distilled water by gavage.The general state of rats was observed;the contents of serum amylase(AMS)and C-reactive protein(CRP)were detected by biochemistry analyzer;the pathological changes of pancreas and lung tissue were observed by HE staining;the contents of TNF-α,IL-1βand IL-6 in lung tissue were detected by ELISA;the expression of PI3K,AKT,Caspase-3,Bcl-2,and Bax mRNA in lung tissue were detected by RT-PCR;the expression of PI3K,p-AKT,Caspase-3,Bcl-2,and Bax protein in lung tissue were detected by Western blot.Results Compared with the blank group,the survival state of the rats in model group was generally poor,the contents of serum AMS and CRP significantly increased(P<0.01),HE staining showed necrosis,hyperemia and incomplete structure of pancreas and lung tissue,the contents of TNF-α,IL-1βand IL-6 in lung tissue significantly increased(P<0.01),the proteins and mRNAs expression of PI3K,Caspase-3 and Bax significantly increased,the protein and mRNA expression of Bcl-2 significantly decreased,the expression of AKT mRNA and p-AKT protein significantly increased(P<0.01).Compared with the model group,the general survival state of rats in each treatment group were improved in varying degrees,the contents of serum AMS and CRP decreased to varying degrees,the degree of edema and necrosis of pancreas and lung tissue were significantly improved,the contents of TNF-α,IL-1βand IL-6 in lung tissue of the rats in octreotide group and Dahuang Mudan Decoction high-and medium-dosage groups significantly decreased(P<0.01,P<0.05),the proteins and mRNAs expression of PI3K,Caspase-3 and Bax in lung tissue of the rats in octreotide group and Dahuang Mudan Decoction high-dosage group decreased significantly,the protein and mRNA expression of Bcl-2 significantly increased,the expression of AKT mRNA and p-AKT protein significantly decreased(P<0.01,P<0.05).Conclusion Dahuang Mudan Decoction has a good improvement effect on acute pancreatitis rats,and its mechanism may be related to inhibiting the PI3K/AKT signaling pathway,reducing the pathological damage of lung tissue,and inhibiting cells apoptosis and inflammatory reaction.

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