番石榴叶总黄酮对慢性胰腺炎小鼠纤维化的影响

王曼雪; 张桂贤; 刘洪斌; 刘大卫; 张一; 李东华; 聂卫

doi:10.13422/j.cnki.syfjx.20181039

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番石榴叶总黄酮对慢性胰腺炎小鼠纤维化的影响

药理 | 更新时间：2024-01-04

- 番石榴叶总黄酮对慢性胰腺炎小鼠纤维化的影响
- Effect of Total Flavonoids from Leaves on Pancreatic Fibrosis of Chronic Pancreatitis Mice
- 中国实验方剂学杂志 2018年24卷第10期页码：175-180
- 作者机构：
- 作者简介：
- 基金信息：
  
  天津市卫生计生委科技基金项目（2014KY39）;天津市自然科学基金项目（17JCYBJC27700）
- DOI：10.13422/j.cnki.syfjx.20181039
  中图分类号： R285.5
- 纸质出版日期：2018
- 稿件说明：
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王曼雪, 张桂贤, 刘洪斌, 等. 番石榴叶总黄酮对慢性胰腺炎小鼠纤维化的影响[J]. 中国实验方剂学杂志, 2018,24(10):175-180.

WANG Man-xue, ZHANG Gui-xian, LIU Hong-bin, et al. Effect of Total Flavonoids from Leaves on Pancreatic Fibrosis of Chronic Pancreatitis Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(10): 175-180.
王曼雪, 张桂贤, 刘洪斌, 等. 番石榴叶总黄酮对慢性胰腺炎小鼠纤维化的影响[J]. 中国实验方剂学杂志, 2018,24(10):175-180. DOI： 10.13422/j.cnki.syfjx.20181039.

WANG Man-xue, ZHANG Gui-xian, LIU Hong-bin, et al. Effect of Total Flavonoids from Leaves on Pancreatic Fibrosis of Chronic Pancreatitis Mice[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(10): 175-180. DOI： 10.13422/j.cnki.syfjx.20181039.

摘要

目的：探讨番石榴叶总黄酮（total flavonoids from Psidium guajava leaves，TFPGL）对慢性胰腺炎（chronic pancreatitis，CP）小鼠纤维化的影响及其机制。方法：将50只C57BL/6小鼠随机均分为正常组，CP模型组，oxidized ATP（oxATP）组，TFPGL低、高剂量组。后4组小鼠腹腔注射雨蛙素50 μg·kg-1·h-1（溶于200 μL生理盐水），每天6次，每周3 d，连续6周，建立慢性胰腺炎小鼠模型。6周后，oxATP组腹腔注射oxATP（15 μg·kg-1·d-1，溶于200 μL生理盐水）2周，TFPGL低、高剂量组分别予以TFPGL 0.186，0.372 g·kg-1·d-1灌胃2周。同时，正常组小鼠腹腔注射与模型组等体积、等频率的生理盐水。苏木素-伊红（HE）染色评估胰腺损伤程度；天狼星红染色检测胰腺组织胶原含量；免疫组化检测α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA），核苷酸结合寡聚化结构域样受体3（nucleotide binding oligomerization domain-like receptor 3，NLRP3），半胱氨酸天冬氨酸蛋白酶-1（cysteinyl aspartate specific proteinase-1，Caspase-1）的蛋白表达水平；酶联免疫吸附法测定胰腺组织中IL-1β（interleukin-1β），IL-18水平。结果：与正常组比较，雨蛙素注射后胰腺损伤加重（P<0.01），Caspase-1，NLRP3，α-SMA，IL-1β，IL-18水平升高（P<0.01）。天狼星红染色显示胰腺组织细胞周围胶原Ⅰ（ColⅠ），胶原Ⅲ（ColⅢ）含量较正常组升高（P<0.01）。与模型组比较，oxATP组及TFPGL低、高剂量组炎症损伤及纤维化程度均减轻，表现为天狼星红染色程度减轻（P<0.05，P<0.01），Caspase-1，NLRP3，α-SMA，IL-1β，IL-18水平均降低（P<0.05，P<0.01）。结论：TFPGL可通过抑制P2X7R介导NLRP3炎性体信号途径活化显著减轻慢性胰腺炎模型小鼠的慢性炎症及纤维化程度。

Abstract

Objective: To investigate the effect and mechanism of total flavonoids from Psidium guajava leaves (TFPGL) on pancreatic fibrosis in a mouse model of chronic pancreatitis (CP). Method: Fifty male C57BL/6 mice were randomly divided into control group

CP model group

oxidized ATP (oxATP) group

high-dose TFPGL group and low-dose TFPGL group. CP model were built in the latter four groups by intraperitoneally injecting 50 μg·kg-1 cerulein (dissolved in 200 μL of physiological saline) per hour

6 times per day

three times per week

for six consecutive weeks.Six weeks later

oxATP (15 μg·kg-1 per day

dissolved in 200 μL of physiological saline) was given to oxATP group through intraperitoneal injection. And 0.186 g·kg-1 per day and 0.372 g·kg-1 per day TFPGL were given by gavage to high-dose TFPGL group and low-dose TFPGL group for two weeks

respectively. Meanwhile

the control group received 0.9% sterile sodium chloride through intraperitoneal injection at the same frequency and volume of the model group.The degree of pancreatic damage was evaluated by HE staining

and the content of pancreatic tissue collagen was detected by Sirius red staining. The expressions of nucleotide binding oligomerization domain like receptor 3 (NLRP3)

cysteinyl aspartate specific proteinase-1 (Caspase-1) and α-smooth muscle actin (α-SMA) were assessed by immunohistochemical staining. The IL-1β and IL-18 levels in pancreatic tissues were measured by an enzyme-linked immunosorbent assay. Result: Compared with the control group

the pancreatic damage aggravated (P<0.01)

and the levels of Caspase-1

NLRP3

α-SMA

IL-1β and IL-18 increased (P<0.01). After injection with caerulein. Picric acid-sirius red staining in pancreatic tissues showed that the pericellular accumulations of collagen I (Col I) and collagen Ⅲ (Col Ⅲ) (P<0.001)

were increased compared with the control group. Compared with the model group

ameliorated inflammatory injury and fibrosis (P<0.05

P<0.01)

were observed in oxATP and TFPGL groups

which was manifested as decrease in degree of picric acid-sirius red staining and levels of Caspase-1

NLRP3

α-SMA

IL-1β and IL-18. Conclusion: TFPGL can alleviate chronic inflammatory reaction and fibrosis in the model mice of chronic pancreatitis

which related to the inhibition of P2X7R-mediated NLRP3 inflammasome activation.

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