目的 观察Janus激酶2/信号转导与转录激活子3（JAK2/STAT3）信号通路在胰蛋白酶原激活肽（TAP）诱导大鼠胰腺腺泡细胞释放高迁移率族蛋白B1（HMGB1）中的作用。方法 提取大鼠胰腺腺泡细胞,随机分为正常对照组、TAP促进组（终质量浓度为3...目的 观察Janus激酶2/信号转导与转录激活子3（JAK2/STAT3）信号通路在胰蛋白酶原激活肽（TAP）诱导大鼠胰腺腺泡细胞释放高迁移率族蛋白B1（HMGB1）中的作用。方法 提取大鼠胰腺腺泡细胞,随机分为正常对照组、TAP促进组（终质量浓度为3 nmol/L）、JAK2抑制剂AG490预处理组（25μ.mol/L）、STAT3抑制剂雷帕霉素预处理组（40μg/L）,采用聚合酶链反应（PCR）及Western blot法检测3-24 h各组HMGB1 mRNA及蛋白表达水平。结果 与正常对照组HMGB1 mRNA表达水平（1.01±0.04）比较,TAP组6-24 h HMGB1 mRNA表达水平显著增高（2.87±0.08、32.85±1.48、38.43±1.60,P〈0.01）,与TAP组比较,AG490预处理组12-24 h HMGB1 mRNA表达均显著抑制（23.40±1.38、19.44±0.89,P〈0.01）,与TAP组比较,雷帕霉素预处理组12-24 h HMGB1 mRNA表达均显著抑制（21.14±1.32、17.76±0.57,P〈0.01）。与正常对照组HMGB1蛋白表达水平（0.39±0.02）比较,TAP组3-24 h HMGB1蛋白表达显著增高（0.46±0.02、0.67±0.03、0.72±0.02、0.90±0.03,P〈0.01）,与TAP组比较,AG490预处理组12-24 h HMGB1蛋白表达均显著抑制（0.60±0.02、0.54±0.01,P〈0.01）,与TAP组比较,雷帕霉素预处理组12-24 h HMGB1蛋白表达均显著抑制（0.59±0.02、0.58±0.01,P〈0.01）。结论 TAP可诱导大鼠胰腺腺泡细胞HMGB1的表达和释放,其机制可能与JAK2/STAT3信号通路有关。展开更多
Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats....Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.展开更多
文摘目的 观察Janus激酶2/信号转导与转录激活子3（JAK2/STAT3）信号通路在胰蛋白酶原激活肽（TAP）诱导大鼠胰腺腺泡细胞释放高迁移率族蛋白B1（HMGB1）中的作用。方法 提取大鼠胰腺腺泡细胞,随机分为正常对照组、TAP促进组（终质量浓度为3 nmol/L）、JAK2抑制剂AG490预处理组（25μ.mol/L）、STAT3抑制剂雷帕霉素预处理组（40μg/L）,采用聚合酶链反应（PCR）及Western blot法检测3-24 h各组HMGB1 mRNA及蛋白表达水平。结果 与正常对照组HMGB1 mRNA表达水平（1.01±0.04）比较,TAP组6-24 h HMGB1 mRNA表达水平显著增高（2.87±0.08、32.85±1.48、38.43±1.60,P〈0.01）,与TAP组比较,AG490预处理组12-24 h HMGB1 mRNA表达均显著抑制（23.40±1.38、19.44±0.89,P〈0.01）,与TAP组比较,雷帕霉素预处理组12-24 h HMGB1 mRNA表达均显著抑制（21.14±1.32、17.76±0.57,P〈0.01）。与正常对照组HMGB1蛋白表达水平（0.39±0.02）比较,TAP组3-24 h HMGB1蛋白表达显著增高（0.46±0.02、0.67±0.03、0.72±0.02、0.90±0.03,P〈0.01）,与TAP组比较,AG490预处理组12-24 h HMGB1蛋白表达均显著抑制（0.60±0.02、0.54±0.01,P〈0.01）,与TAP组比较,雷帕霉素预处理组12-24 h HMGB1蛋白表达均显著抑制（0.59±0.02、0.58±0.01,P〈0.01）。结论 TAP可诱导大鼠胰腺腺泡细胞HMGB1的表达和释放,其机制可能与JAK2/STAT3信号通路有关。
基金supported by the Young Scientists Foundation of Hubei Provincial Health Department,No.QJX2012-16
文摘Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae （Gegen）, has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment （intravenous injection） re- duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-a in brain tissue. Pretreatment with puerarin （intravenous injection） attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 （JAK2） and signal transducers and activators of transcription 3 （STAT3） activation and nuclear factor kappa B （NF-KB） inhibition. These observa- tions were inhibited by the alpha7 nicotinic acetylcholine receptor （a7nAchR） antagonist a-bungarotoxin （a-BGT）. In addition, puerarin pretreatment increased the expression of a7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re- sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be medi- ated through the activation of the cholinergic anti-inflammatory pathway.
