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1谷氨酸通过调控脊髓背角GABA_(B)R2参与慢性胰腺炎痛的机制研究显示文摘目的探讨谷氨酸通过调控脊髓背角GABA_(B)R2参与慢性胰腺炎(chronic pancreatitis,CP)疼痛的机制研究,为缓解慢性胰腺炎痛寻找新的理论依据。方法将42只Wistar雄性大鼠(约200 g)分为对照组(n=12)和CP组(n=30)。CP组尾静脉单次注射二丁基二氯化合物(DBTC,8 mg·kg^(-1))构建CP模型,对照组注射溶剂。通过HE染色明确胰腺组织病理特征改变。利用Von Frey电子测痛仪测定每组大鼠在注射前和注射后3、7、14、21 d的腹部机械痛。Western-blot及免疫荧光组织化学检测大鼠T8—T12节段脊髓背角、体外培养脊髓背角神经元上GABA_(B)R2的表达。结果CP模型大鼠胰腺组织可见散在腺泡细胞肿胀坏死,广泛的炎症细胞浸润及大量纤维结缔组织增生。与对照组比较:CP组大鼠腹部机械痛阈值明显下降,并持续至DBTC注射后21 d(P<0.05,P<0.001);在DBTC注射后7、14、21 d脊髓背角GABA_(B)R2的表达明显减少(P<0.001)。体外实验结果表明,原代培养的脊髓背角神经元经20、40μmol·L^(-1)谷氨酸处理后,GABA_(B)R2的表达均明显减少(P<0.001)。结论谷氨酸通过调控脊髓背角神经元GABA_(B)R2的表达是CP疼痛发生的机制之一。徐卉红 邱海波 王莉琴 朱成成 陆智杰 2022南昌大学学报(医学版)2022,62,4:0
2YAP activates pancreatic stellate cells and enhances pancreatic fibrosis显示文摘Background:Pancreatic stellate cells(PSCs)foster the progression of pancreatic adenocarcinoma and chronic pancreatitis(CP)by producing a dense fibrotic stroma.However,the incomplete knowledge of PSCs biology hampers the exploration of antifibrotic therapies.Here,we explored the role of the Hippo pathway in the context of PSCs activation and experimental CP.Methods:CP model was created in rats with the tail vein injection of dibutyltin dichloride(DBTC).The expression of Yes-associated protein(YAP)in CP tissue was assessed.Primary and immortalized rats PSCs were treated with the YAP-inhibitor verteporfin.Furthermore,YAP siRNA was employed.Subsequently,DNA synthesis,cell survival,levels ofα-smooth muscle actin(α-SMA)protein,presence of lipid droplets and PSCs gene expression were evaluated.Upstream regulators of YAP signaling were studied by reporter gene assays.Results:In DBTC-induced CP,pronounced expression of YAP in areas of tubular structures and periduc-tal fibrosis was observed.Verteporfin diminished DNA replication in PSCs in a dose-dependent fash-ion.Knockdown of YAP reduced cell proliferation.Primary cultures of PSCs were characterized by a de-crease of lipid droplets and increased synthesis ofα-SMA protein.Both processes were not affected by verteporfin.At the non-cytotoxic concentration of 100 nmol/L,verteporfin significantly reduced mRNA levels of transforming growth factor-β1(Tgf-β1)and Ccn family member 1(Ccn1).YAP signaling was acti-vated by TGF-β1,but repressed by interferon-γ.Conclusions:Activated YAP enhanced PSCs proliferation.The antifibrotic potential of Hippo pathway in-hibitors warrants further investigation.Lennard Spanehl Denis Revskij Karen Bannert Luise Ehlers Robert Jaster 2022Hepatobiliary & Pancreatic Diseases International2022,21,6:0
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