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| Study on the mechanism of Tanshinone ⅡA alleviates gastric mucosal injury in rats with chronic atrophic gastritis by inhibiting JAK2/STAT3 pathway |
| Hits 201 Download times 130 Received:January 20, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2024.07.19 |
| Key Words
chronic atrophic gastritis;Tanshinone ⅡA;gastric mucosa;inflammation;apoptosis;JAK2/STAT3 pathway |
| Author Name | Affiliation | | REN Liang | Handan Central Hospital, Handan 056001, China | | WANG Libin | Handan Shexian Hospital, Handan 056400, China | | ZHANG Min | Handan Central Hospital, Handan 056001, China |
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| Abstract
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| [Objective] To investigate the effect of Tanshinone ⅡA（Tan ⅡA） on gastric mucosa in rats with chronic atrophic gastritis（CAG），and explore its mechanism based on the janus kinase 2/signal transduction and transcriptional activator 3（JAK2/STAT3） pathway. [Methods] The 80 Wistar rats were randomly divided into 5 groups（n=16）：Normal group，Model group，Tan ⅡA（5 mg/kg） group，Tan ⅡA（5 mg/kg） + AG490（JAK2 inhibitor，5 mg/kg） group and Tan ⅡA（5 mg/kg） + C-A1（JAK2 agonist，50 mg/kg） group. Except for normal group，the rats in other 4 groups were treated with free drinking of N-methyl-N’-nitro-N-nitroguanidine solution（MNNG， 0.04 g/mL） combined with ranitidine gavage and starvation and satiety disorder diet. After 12 weeks of continuous administration once a day in each group，the gastric mucosal blood flow was detected by neutral red clearance. The gastrin（GAS） in serum，motilin（MTL） in plasma and the inflammatory factors in gastric mucosa were detected by ELISA. The gastric mucosal histopathological changes was observed through HE staining，and the atrophy score was performed. The apoptosis of gastric mucosa cells was observed through TUNEL staining，and the apoptosis index was calculated. The mRNA and protein expression of JAK2/STAT3 pathway in gastric mucosa were detected by RT-PCR or Western blotting. [Results] Compared with the Model group，the gastric mucosal blood flow，the level of GAS in serum and the level of MTL in plasma of Tan ⅡA group were significantly increased（P<0.05）. The level of tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β），IL-6 in gastric mucosa were significantly decreased（P<0.05）. The pathological changes of gastric mucosa were significantly improved，and the atrophy score was significantly decreased（P<0.05）. The number of apoptotic cells was decreased significantly，and the apoptotic index was significantly decreased（P<0.05）. The mRNA expressions of JAK2，STAT3 in gastric mucosa were significantly decreased（P<0.05）. The expression of B lymphoblastoma 2（Bcl-2） protein was significantly increased（P<0.05）. The protein expression level of Bcl-2 associated X protein（Bax），cleaved Caspase-3（C-Cas-3），cleaved Caspase-9（C-Cas-9） and the ratio of P-JAK2/JAK2，P-STAT3/STAT3，nuclear NF-κB p65/cytoplasmic NF-κB p65 were significantly decreased（P<0.05）. AG490 could significantly enhance the regulatory effect of Tan ⅡA on various detection indexes in CAG rats，and C-A1 could significantly reverse the regulatory effect of Tan ⅡA on CAG rats（P<0.05）. [Conclusion] Tan ⅡA can reduce the structural and functional damage of gastric mucosa in CAG rats by inhibiting JAK2/STAT3 pathway activation and NF-κB nuclear translocation，and reducing inflammatory response and apoptosis. |
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