西红花苷对重症胰腺炎大鼠炎症反应及细胞凋亡水平的抑制作用

Inhibitory Effect of Crocin on Inflammatory Response and Apoptosis in Rats with Severe Pancreatitis

目的:探讨西红花苷对重症胰腺炎大鼠炎症反应及细胞凋亡水平的抑制作用。方法:32只大鼠随机分为假手术组、模型组、西红花苷低剂量组、西红花苷高剂量组,每组8只。逆行胆管注射5%牛黄胆酸钠建立重症胰腺炎模型,造模成功后,西红花苷低、高剂量组大鼠分别尾静脉注射25、50 mg/kg西红花苷溶液,假手术组、模型组大鼠尾静脉注射等量生理盐水,连续注射1周。通过HE染色观察各组大鼠胰腺组织病理变化,ELISA试剂盒检测各组大鼠血清淀粉酶、TNF-α、IL-1β、IL-6含量,TUNEL检测各组大鼠胰腺组织细胞凋亡率,RT-qPCR和Western-blotting检测各组大鼠胰腺组织Janus蛋白酪氨酸激酶2/信号转导和转录激活子3(JAK2/STAT3)信号通路及凋亡相关指标的表达水平。结果:与假手术组比较,模型组大鼠胰腺组织出现大量炎症细胞浸润、间质水肿及组织坏死,胰腺组织细胞凋亡率,凋亡相关蛋白Bcl-2相关X蛋白(Bax)、裂解的半胱氨酸天冬氨酸蛋白酶3(cleaved-Caspase-3)表达,血清淀粉酶,各炎症因子含量,胰腺组织JAK2/STAT3信号通路相关指标表达水平均升高(P<0.05);西红花苷干预后,大鼠胰腺组织炎症细胞浸润显著减少,水肿以及组织坏死得到改善,细胞凋亡率Bax、cleaved-Caspase-3蛋白表达,血清淀粉酶,各炎症因子含量,JAK2/STAT3信号通路相关指标表达水平均显著下降(P<0.05)。结论:西红花苷能够抑制重症胰腺炎大鼠炎症反应及细胞凋亡,对重症胰腺炎大鼠起到保护作用,其机制可能与西红花苷抑制JAK2/STAT3信号通路有关。

Objective:To investigate the inhibitory effect of crocin on the inflammatory response and apoptosis of rats with severe pancreatitis.Methods:A total of 32 rats were randomly divided into sham operation group,model group,crocin low-dose group,and crocin high-dose group,with 8 rats in each group.The model of severe pancreatitis was established by retrograde bile duct injection with 5%sodium taurocholate.After successful modeling,rats in crocin low and high-dose group were injected with 25,50 mg/kg crocin solution in the tail vein,respectively.The rats in the sham operation group and the model group were injected with the same amount of normal saline in the tail vein for 1 week.The pathological changes of rat pancreas tissues in each group were observed by HE staining.The content of serum amylase,TNF-α,IL-1β,IL-6 in each group were detected by ELISA kit.The apoptosis rate of pancreatic tissue in each group was detected by TUNEL.RT-qPCR and Western blotting were used to detect the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway and apoptosis related indicators in pancreatic tissue.Results:Compared with the sham operation group,a large number of inflammatory cell infiltration,interstitial edema and tissue necrosis appeared in the pancreatic tissue of the model group.The apoptosis rate of pancreatic tissue cell,the expression of apoptosis related protein Bax,cleaved Caspase-3,the content of serum amylase,inflammatory factors and the expression of JAK2/STAT3 signaling pathway in pancreatic tissue of model group were higher than those of sham operation group(P<0.05).After the intervention of crocin,the inflammatory infiltration of rat pancreatic tissue was significantly reduced,and the edema and tissue necrosis were improved.The apoptosis rate of pancreatic tissue cell,the expression of apoptosis related protein Bax,cleaved Caspase-3,the content of serum amylase,inflammatory factors and the expression of JAK2/STAT3 signaling pathway in pancreatic tissue of crocin low and high-dose group were higher than those of model group(P<0.05).Conclusion:Crocin can inhibit the inflammatory response and cell apoptosis in severe pancreatitis rats,and play a protective role in severe pancreatitis rats.The mechanism may be related to the inhibition of JAK2/STAT3 signaling pathway by crocin.