Effects of parthenolide on systemic inflammation and intestinal injury in rats with acute pancreatitis
- VernacularTitle:小白菊内酯对急性胰腺炎大鼠全身炎症及肠道损伤的影响
- Author:
Yanan ZHAO
1
;
Rui ZHANG
2
;
Shuling WANG
3
;
Chunchun YANG
1
;
Yang WANG
3
;
Mingyue YANG
1
Author Information
1. Dept. Two of Gastroenterology Diagnosis and Treatment，the First Hospital of Hebei Medical University，Shijiazhuang 050023，China
2. Dept. Four of Gastroenterology Diagnosis and Treatment，the First Hospital of Hebei Medical University，Shijiazhuang 050023，China
3. Dept. Three of Gastroenterology Diagnosis and Treatment，the First Hospital of Hebei Medical University，Shijiazhuang 050023，China
- Publication Type:Journal Article
- Keywords:
parthenolide;
acute pancreatitis;
inflammation;
intestinal injury;
Keap1/Nrf2/HO-1 signaling pathway
- From:
China Pharmacy
2025;36(6):704-709
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of parthenolide （PLT） on systemic inflammation and intestinal injury in rats with acute pancreatitis （AP） by regulating the Kelch-like epichlorohydrin-associated protein 1 （Keap1）/nuclear factor-erythroid-2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. METHODS AP rat model was established by injecting 3.5% sodium taurine cholate solution （1 mL/kg） into the biliary pancreatic duct， and modeled rats were divided into AP group， PLT （300 µg/kg） group， dexamethasone （2 mg/kg） group， inhibitor （11 mg/kg Nrf2 inhibitor ML385） group， and PLT+inhibitor group （300 µg/kg PLT+11 mg/kg ML385）， with 10 rats in each group. Another 10 rats were taken as a sham operation group. Each group was given relevant medicine or normal saline via tail vein/intraperitoneal injection once. After 24 h， serum lipase and amylase levels， the levels of oxidative stress index [superoxide dismutase （SOD） and malondialdehyde （MDA）] and inflammatory factors [interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α）] were detected. The histopathological changes in colon mucosa and pancreas were observed， and Chiu and Schmidt scores were performed. The cell apoptosis in colon mucosa and the protein expressions of Keap1， Nrf2 and HO-1 were detected. RESULTS Compared with the sham operation group， there was obvious inflammatory cell infiltration in colon mucosa and pancreatic tissue， cell shedding or tissue necrosis and severe bleeding； serum levels of lipase， amylase， MDA， IL-1β， IL-6 and TNF-α， Chiu and Schmidt scores， apoptotic rate and protein expression of Keap1 in colonic mucosa were significantly increased or up-regulated， while SOD level and protein expressions of Nrf2 20230993） and HO-1 were decreased or down-regulated significantly （P＜0.05）. Compared with the AP group， the above indexes in the PLT group and dexamethasone group were significantly improved， while those in the inhibitor group further deteriorated （P＜0.05）. Inhibitor could significantly reverse the improvement effect of PLT on the above indexes in AP rats （P＜ 0.05）. CONCLUSIONS PLT inhibits inflammation and oxidative stress in AP rats， alleviates intestinal damage， and its mechanism may be related to inhibiting protein expression of Keap1 and activating Nrf2/HO-1 signaling pathway.
