Chaihu Guizhitang Attenuates Neuropathic Abdominal Pain of Chronic Pancreatitis
10.13422/j.cnki.syfjx.20221407
- VernacularTitle:柴胡桂枝汤减轻慢性胰腺炎神经性腹痛机制的探讨
- Author:
Sainan LI
1
;
Guixian ZHANG
2
;
Hongsheng SHEN
2
;
Manxue WANG
2
;
Xijing LI
2
;
Xia LI
2
;
Wenchang LI
2
;
Yi XIAO
1
;
Hongbin LIU
2
Author Information
1. Graduate School, Tianjin Medical University,Tianjin 300070,China
2. Tianjin Institute of Medical and Pharmaceutical Sciences,Tianjin 300020,China
- Publication Type:Journal Article
- Keywords:
chronic pancreatitis;
Chaihu Guizhitang;
microglia;
macrophages;
neuropathic pain;
neuritis;
purinergic receptor P2X7 (P2RX7)
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(22):40-46
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of Chaihu Guizhitang (CHGZT) in alleviating neuropathic abdominal pain induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in rats with chronic pancreatitis (CP). MethodFifty male SD rats were randomly assigned into five groups: sham operation, CP model, and low-, medium-, and high-dose (4, 8, and 16 g·kg-1, respectively) CHGZT groups. In the sham operation group, the abdomen was closed after the pancreas was gently stirred. The rat model of CP was established by retrograde injection of 2% TNBS-10% ethanol into the pancreatic duct. The oral administration of CHGZT started 4 weeks after modeling and lasted for 2 weeks. Pain threshold was measured by Von Frey fibers 6 weeks after surgery. Hematoxylin-eosin (HE) staining was employed to reveal the chronic inflammation and fibrosis of the pancreatic tissue. Immunohistochemmistry (IHC) was employed to detect the expression of PGP9.5 (a marker of pancreatic nerves) and reveal the inflammatory changes around the nerves. IHC and immunofluorescence (IF) were used to determine the location of ionized calcium-binding adaptor molecule-1 (Iba-1, microglia marker) and purinergic receptor P2X7 (P2RX7) and the co-expression of P2RX7 and Iba-1 in the thoracic spinal dorsal horn. ResultCompared with the sham operation group, the modeling increased the scores of pancreatic gland atrophy, inflammatory infiltration, and fibrosis (P<0.01), the abdominal pain response under different force values (P<0.05, P<0.01), and the score of peripancreatic inflammation. Moreover, the modeling up-regulated the expression of Iba-1 and P2RX7 in the thoracic spinal dorsal horn (P<0.01). Compared with the model group, the high- and medium-dose CHGZT lowered the scores of pancreatic gland atrophy, inflammatory infiltration, and fibrosis, the abdominal pain response, and the score of peripancreatic inflammation (P<0.05, P<0.01). The high-, medium-, and low-dose CHGZT all down-regulated the expression of Iba-1 and P2RX7 (P<0.01). ConclusionCHGZT can significantly relieve abdominal pain in CP rat by suppressing the inflammation around nerves in the pancreas and the P2RX7 activation of microglia in the spinal dorsal horn.