Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-<italic style="font-style: italic">κ</italic>B/NLRP3/IL-1<italic style="font-style: italic">β</italic> Signaling Pathway

ZOU Yuqing; SHI Hong; LIU Xin; ZHUANG Shuting; ZHANG Jialin; CHEN Jiamin; ZHANG Jieping

doi:10.13422/j.cnki.syfjx.20231064

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Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway

更新时间：2023-08-22

- Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 18, Pages: 78-86(2023)
- 作者机构：
  
  1.福建中医药大学，福州 350000
  2.福建中医药大学附属第三人民医院，福州 350000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20231064
  CLC： R22;R587.1;R28;R96
- Received：15 March 2023，
  
  Published Online：28 May 2023，
  
  Published：20 September 2023
- 稿件说明：
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邹玉卿,施红,刘欣等.基于NF-κB/NLRP3/IL-1β信号通路探讨石斛合剂对糖尿病伴非酒精性脂肪性肝病大鼠细胞炎症反应及凋亡的作用[J].中国实验方剂学杂志,2023,29(18):78-86.

ZOU Yuqing,SHI Hong,LIU Xin,et al.Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(18):78-86.
邹玉卿,施红,刘欣等.基于NF-κB/NLRP3/IL-1β信号通路探讨石斛合剂对糖尿病伴非酒精性脂肪性肝病大鼠细胞炎症反应及凋亡的作用[J].中国实验方剂学杂志,2023,29(18):78-86. DOI： 10.13422/j.cnki.syfjx.20231064.

ZOU Yuqing,SHI Hong,LIU Xin,et al.Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(18):78-86. DOI： 10.13422/j.cnki.syfjx.20231064.

摘要

目的

探讨石斛合剂对糖尿病伴非酒精性脂肪肝模型大鼠细胞炎症性反应及凋亡的影响及可能作用机制。

方法

雄性SD大鼠40只，按体质量随机分为空白组10只和2型糖尿病（T2DM）伴非酒精性脂肪性肝病（NAFLD）模型组30只。采用高糖高脂饮食联合腹腔注射链脲佐菌素（STZ）建立模型，按血糖、体质量随机分为模型组，石斛合剂组（16.67 g·kg

-1

·d

-1

），二甲双胍组（100 mg·kg

-1

·d

-1

），每组10只，按剂量连续灌胃给药4周，空白组与模型组灌胃按10 mL·kg

-1

·d

-1

给予生理盐水。检测各组大鼠空腹血糖（FBG）、血清胰岛素（INS）、糖化血清蛋白（GSP）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）等指标。各组大鼠肝组织采用苏木素-伊红（HE）染色观察病理改变，免疫组织化学法观察核转录因子（NF）-

B、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、白细胞介素（IL）-1

、肿瘤坏死因子（TNF）-

阳性表达。蛋白免疫印迹法（Western blot）、实时荧光定量聚合酶链式反应（Real-time PCR）检测各组大鼠肝组织B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、胱天蛋白酶-3（Caspase-3）、NF-

B p65（NF-

B p65）、NLRP3、IL-1

、TNF-

的蛋白及mRNA表达情况。

结果

与空白组比较，模型组FBG、GSP、TC、TG、LDL-C、AST、ALT均上升，INS、HDL-C下降，Bax、Caspase-3、NLRP3、IL-1

、TNF-

蛋白及mRNA表达上升，p-NF-

B/NF-

B蛋白上升，Bcl-2蛋白及mRNA表达下降，NF-

B、NLRP3、IL-1

、TNF-

免疫组化阳性表达升高，差异有统计学意义（

0.01），肝脏形态结构被破坏，可见明显脂肪空泡。与模型组比较，石斛合剂组与二甲双胍组FBG、GSP、TC、TG、LDL-C、AST、ALT均下降，INS、HDL-C上升，Bax、Caspase-3、NLRP3、IL-1

、TNF-

蛋白及mRNA表达下降，p-NF-

B/NF-

B蛋白下降，Bcl-2蛋白及mRNA表达升高，NF-

B、NLRP3、IL-1

、TNF-

免疫组化阳性表达下降，差异具有统计学意义（

0.01），肝脏形态结构较为完整，脂肪空泡减少。

结论

石斛合剂对T2DM伴NAFLD大鼠具有抑制细胞凋亡、减轻炎症反应、缓解肝损伤作用，其机制可能与抑制NF-

B通路激活，阻滞NLRP3炎症小体激活，减少IL-1

分泌，减弱Caspase-3活性，降低Bcl-2/Bax有关。

Abstract

Objective

To investigate the effect of Dendrobii Caulis mixture on cell inflammatory response and apoptosis in diabetic rat with non-alcoholic fatty liver disease（NAFLD） and its possible mechanism.

Method

Forty male SD rats were randomly divided into blank group and model group of type 2 diabetes mellitus（T2DM） with NAFLD according to body weight. The model was established by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ）， which was randomly divided into the model group， Dendrobii Caulis mixture group（16.67 g·kg

-1

·d

-1

） and metformin group（100 mg·kg

-1

·d

-1

） according to blood glucose and body weight， and 10 rats in each group. Rats in each group were administered by continuous gavage for 4 weeks， the blank and model groups were given saline by gavage at 10 mL·kg

-1

·d

-1

. Fasting blood glucose（FBG）， serum insulin（INS）， glycosylated serum protein（GSP）， triglyceride（TG）， total cholesterol（TC）， high density lipoprotein（HDL-C）， low density lipoprotein（LDL-C）， alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were detected in each group of rats. The liver tissues of rats in each group were stained with hematoxylin-eosin（HE） to observe the pathological changes， and the positive expressions of nuclear transcription factor（NF）-

B， NOD-like receptor heat protein structural domain-related protein 3（NLRP3）， interleukin（IL）-1

and tumor necrosis factor（TNF）-

were observed by immunohistochemistry. Western blot and fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression of B-cell lymphoma-2（Bcl-2）， Bcl-2 associated X protein（Bax）， Caspase-3 and NF-

B p65， NLRP3， IL-1

， TNF-

in liver tissue of rats in each group.

Result

Compared with the blank group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels were increased， INS and HDL-C levels were decreased， Bax， Caspase-3， NLRP3， IL-1

， TNF-

protein and mRNA expression were increased in model group， the ratio of p-NF-

B/NF-

B protein increased， the expression of Bcl-2 protein and mRNA decreased， and the positive immunohistochemical expression of NF-

B， NLRP3， IL-1

and TNF-

increased， and the differences were statistically significant（

0.01）. The morphological structure of the liver was disrupted， and obvious fat vacuoles were seen. Compared with the model group， FBG， GSP， TC， TG， LDL-C， AST and ALT levels of Dendrobii Caulis mixture group and metformin group were decreased， INS and HDL-C levels were increased， and protein and mRNA expressions of Bax， Caspase-3， NLRP3， IL-1

and TNF-

were decreased， the protein ratio of p-NF-

B/NF-

B decreased， the expression of Bcl-2 protein and mRNA increased， and the positive immunohistochemical expressions of NF-

B， NLRP3， IL-1

and TNF-

decreased， and the differences were statistically significant（

0.01）. The liver morphology and structure were relatively complete， and the fat vacuoles were reduced.

Conclusion

Dendrobii Caulis mixture can inhibit cell apoptosis， reduce inflammatory response and alleviate liver injury in rats with T2DM and NAFLD， the mechanism may be related to inhibiting the activation of NF-

B pathway， blocking the activation of NLRP3 inflammatory vesicles， reducing IL-1

secretion， attenuating Caspase-3 activity and reducing the ratio of Bcl-2/Bax.

关键词

Keywords

references

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Effect of Dendrobii Caulis Mixture on Cell Inflammatory Response and Apoptosis in Diabetic Rats with Nonalcoholic Fatty Liver Disease Based on NF-κB/NLRP3/IL-1β Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20231064

摘要

Abstract

关键词

Keywords

references