盐酸戊乙奎醚对肝缺血再灌注致肺损伤的保护作用
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摘要
目的探讨盐酸戊乙奎醚(长托宁)对肝缺血再灌注损伤(HIRI)致急性肺损伤(ALI)影响及其可能的机制。方法选取32只SD大鼠随机分为四组:假手术组(S组)、HIRI致ALI组(IR组)、阿托品预处理组(A组)和长托宁预处理组(P组),每组8只。各组动物"安乐"处死后,光镜下观察肺组织形态学变化;检测肺组织湿/干质量比(W/D);免疫组织化学和Western印迹测定wnt3a和β-catenin蛋白表达。结果与S组比较,IR组、A组和P组wnt3a和β-catenin蛋白表达水平及肺湿干重比升高(P<0.05);与IR组、A组比较,P组肺W/D值、wnt3a、β-catenin表达水平降低,差异有统计学意义(P<0.05)。A组与IR组比较,肺W/D值及wnt3a、β-catenin表达水平差异无统计学意义(P>0.05)。P组与IR组、A组比较肺组织病理形态损伤较轻。结论盐酸戊乙奎醚(长托宁)预给药可通过下调Wnt/β-catenin信号通路减轻肝缺血再灌注损伤所致的急性肺损伤。
Objective To study the effect of penehyclidine hydrochloride on hepatic ischemia/reperfusion injury(HIRI)induced-acute lung injury(ALI) and their potential treatment mechanism in rats. Methods Thirty-two SD rats were randomly divided into four groups, with 8 rats each. The rats in group S were served as sham injury control, and those in group IR underwent 180 min reperfusion after 30 min total hepatic ischemia by clamping the hepatic hilum. The rats in group A and group P were given atropine 2 mg/kg and penehyclidine hydrochloride 2 mg/kg, respectively before the hepatic hilum occlusion, which was followed by group IR. The rats were sacrificed at the end point of the operation and the wet/dry(W/D) weight ratio of lung tissue was measured. Then the lung tissues were divided into several parts for pathological section and the pathological and morphological changes analysis by electron microscopy. The pulmonary wnt3 a and β-catenin activity were examined by Western blotting and immunohistochemistry, respectively. Results Compared with the group S,the lung W/D ratio and the expression of wnt3 a and β-catenin protein in group IR, group A and P were significantly increased(P<0.05). But the lung W/D ratio and the expression of wnt3 a and β-catenin protein in group P were lower than those in group IR and A(P<0.05). Comparing group A and group IR, the lung W/D ratio and the expression of wnt3 a and β-catenin protein had no significant differences(P>0.05). Group P was relatively minor in the pathological morphological of lung tissue compared with group IR and group A. Conclusion Penehyclidine hydrochloride might play a protective part in HIRI induced-ALI by inhibiting Wnt/β-catenin signaling pathway.
Objective To study the effect of penehyclidine hydrochloride on hepatic ischemia/reperfusion injury(HIRI)induced-acute lung injury(ALI) and their potential treatment mechanism in rats. Methods Thirty-two SD rats were randomly divided into four groups, with 8 rats each. The rats in group S were served as sham injury control, and those in group IR underwent 180 min reperfusion after 30 min total hepatic ischemia by clamping the hepatic hilum. The rats in group A and group P were given atropine 2 mg/kg and penehyclidine hydrochloride 2 mg/kg, respectively before the hepatic hilum occlusion, which was followed by group IR. The rats were sacrificed at the end point of the operation and the wet/dry(W/D) weight ratio of lung tissue was measured. Then the lung tissues were divided into several parts for pathological section and the pathological and morphological changes analysis by electron microscopy. The pulmonary wnt3 a and β-catenin activity were examined by Western blotting and immunohistochemistry, respectively. Results Compared with the group S,the lung W/D ratio and the expression of wnt3 a and β-catenin protein in group IR, group A and P were significantly increased(P<0.05). But the lung W/D ratio and the expression of wnt3 a and β-catenin protein in group P were lower than those in group IR and A(P<0.05). Comparing group A and group IR, the lung W/D ratio and the expression of wnt3 a and β-catenin protein had no significant differences(P>0.05). Group P was relatively minor in the pathological morphological of lung tissue compared with group IR and group A. Conclusion Penehyclidine hydrochloride might play a protective part in HIRI induced-ALI by inhibiting Wnt/β-catenin signaling pathway.
引文
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[10]Niell N,Larriba MJ,Ferrermayorga G,et al.The human PKP2/Plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts[J].Int J Cancer,2018,142(4):792-804..
[11]Wang Y,Viennet C,Robin S,et al.Precise role of dermal fibroblasts on melanocyte pigmentation[J].J Dermatol Sci,2017,88(2):159-166.
[12]Mullin NK,Mallipeddi NV,Hamburg-Shields E,et al.Wnt/β-catenin signaling pathway regulates specific lnc RNAs that impact dermal fibroblasts and skin fibrosis[J].Front Genet,2017,8:183.
[13]Hummler SC,Rong M,Chen S,et al.Targeting glycogen synthase kinase-3βto prevent hyperoxia-induced lung injury in neonatal rats[J].Am J Respir Cell Mol Biol,2013,48(5):578-588.
[14]Wang C,Zhu H,Sun Z,et al.Inhibition of Wnt/β-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury[J].Am JPhysiol Cell Physiol,2014,307(3):C234-C244.
[2]CannistràM,Ruggiero M,Zullo A,et al.Hepatic ischemia reperfusion injury:a systematic review of literature and the role of current drugs and biomarkers[J].Int J Surg,2016,33 Suppl1:S57-S70.
[3]吴晓静,冷燕,高文蔚,等.盐酸戊乙奎醚对胸部创伤-失血性休克复苏致大鼠急性肺损伤时NF-κB和AP-1活性的影响[J].中华麻醉学杂志,2015,35(6):751-754.Wu XJ,Leng Y,Gao WW,et al.Effects of penehyclidine hydrochloride on activities of NF-κB andAP-1 during actue lung injury induced by blunt chest traumahemorrhagic shock and resuscitation in rats[J].Chin JAnesthesiol,2015,35(6):751-754.
[4]Maehara S,Adachi E,Shimada M,et al.Clinical usefulness of biliary scope for Pringle’s maneuver in laparoscopic hepatectomy[J].J Am Coll Surg,2007,205(6):816-818.
[5]Liu YY,Chiang CH,Hung SC,et al.Hypoxia-preconditioned mesenchymal stem cells ameliorate ischemia/reperfusion-induced lung injury[J].PLo S One,2017,12(11):e0187637.
[6]孙明立,赵海山,肖庆环,等.β-catenin在乳腺癌中的不同表达定位与预后的关系[J].热带医学杂志,2015,15(6):717-720,863.Sun ML,Zhao HS,Xiao QH,et al.Different expression pattern ofβ-catenin in breast cancer and relationship with prognosis[J].J Trop Med,2015,15(6):717-720,863.
[7]Silvagarcía O,Valdezalarcón JJ,Baizabalaguirre VM.The Wnt/β-catenin signaling pathway controls the inflammatory response in infections caused by pathogenic bacteria[J].Mediators Inflamm,2014,2014:310183.
[8]Peng Y,Cao J,Yao XY,et al.TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/β-catenin signaling[J].Oncotarget,2017,8(32):52960-52974.
[9]Wang X,Xu K,Yang XY,et al.Upregulated mi R-29c1050suppresses silica-induced lung fibrosis through the Wnt/β-catenin pathway in mice[J].Hum Exp Toxicol,2017,1:960327117741750.
[10]Niell N,Larriba MJ,Ferrermayorga G,et al.The human PKP2/Plakophilin-2 gene is induced by Wnt/β-catenin in normal and colon cancer-associated fibroblasts[J].Int J Cancer,2018,142(4):792-804..
[11]Wang Y,Viennet C,Robin S,et al.Precise role of dermal fibroblasts on melanocyte pigmentation[J].J Dermatol Sci,2017,88(2):159-166.
[12]Mullin NK,Mallipeddi NV,Hamburg-Shields E,et al.Wnt/β-catenin signaling pathway regulates specific lnc RNAs that impact dermal fibroblasts and skin fibrosis[J].Front Genet,2017,8:183.
[13]Hummler SC,Rong M,Chen S,et al.Targeting glycogen synthase kinase-3βto prevent hyperoxia-induced lung injury in neonatal rats[J].Am J Respir Cell Mol Biol,2013,48(5):578-588.
[14]Wang C,Zhu H,Sun Z,et al.Inhibition of Wnt/β-catenin signaling promotes epithelial differentiation of mesenchymal stem cells and repairs bleomycin-induced lung injury[J].Am JPhysiol Cell Physiol,2014,307(3):C234-C244.