中华肝胆外科杂志
中華肝膽外科雜誌
중화간담외과잡지
CHINESE JOURNAL OF HEPATOBILIARY SURGERY
2012年
6期
462-465
,共4页
磷脂酰肌醇3-激酶γ%蛙皮素%急性胰腺炎%细胞坏死
燐脂酰肌醇3-激酶γ%蛙皮素%急性胰腺炎%細胞壞死
린지선기순3-격매γ%와피소%급성이선염%세포배사
Phosphatidylinositide 3 kinase gamma%Cerulean%Acute pancreatitis%Cell necrosis
目的 研究磷脂酰肌醇3-激酶γ(P13Kγ)在实验性急性胰腺炎腺泡细胞坏死中的作用,并探讨其作用机制.方法 12只雄性野生型C57BL/6小鼠和12只雄性P13Kγ基因敲除小鼠随机分为对照组和胰腺炎组,腹腔内分别注射生理盐水和蛙皮素(50tμg/kg)诱导急性胰腺炎模型.观察两种动物模型胰腺组织病理变化,同时检测血清胰蛋白酶活性、组织蛋白酶B和L活性的变化,Western blotting检测组织蛋白酶B和L蛋白的表达.结果 组织学显示,P13Kγ基因敲除小鼠胰腺炎腺泡细胞坏死数量[(2.25±0.54)/HP比(5.14±0.85)/HP]和空泡数量[(1.24±0.21)/HP比(2.36±0.34)/HP]明显少于野生型小鼠(P＜0.05),组织蛋白酶B[(1232±21)pmolAMC/min.mg 比(1891±35) pmolAMC/min/mg]和胰蛋白酶活性[(0.358±0.098)pmol/mg比(0.827±0.126)pmol/mg]低于野生型小鼠(P＜0.05),而组织蛋白酶L活性相反[(415±11)pmolAMC/min/mg比(346 ±6) pmolAMC/min/mg] (P＜0.01).结论 P13Kγ在急性胰腺炎时可能具有促进细胞坏死的作用,其可能机制是改变了组织蛋白酶B和L之间的平衡和促进了胰蛋白酶原的活化.
目的 研究燐脂酰肌醇3-激酶γ(P13Kγ)在實驗性急性胰腺炎腺泡細胞壞死中的作用,併探討其作用機製.方法 12隻雄性野生型C57BL/6小鼠和12隻雄性P13Kγ基因敲除小鼠隨機分為對照組和胰腺炎組,腹腔內分彆註射生理鹽水和蛙皮素(50tμg/kg)誘導急性胰腺炎模型.觀察兩種動物模型胰腺組織病理變化,同時檢測血清胰蛋白酶活性、組織蛋白酶B和L活性的變化,Western blotting檢測組織蛋白酶B和L蛋白的錶達.結果 組織學顯示,P13Kγ基因敲除小鼠胰腺炎腺泡細胞壞死數量[(2.25±0.54)/HP比(5.14±0.85)/HP]和空泡數量[(1.24±0.21)/HP比(2.36±0.34)/HP]明顯少于野生型小鼠(P＜0.05),組織蛋白酶B[(1232±21)pmolAMC/min.mg 比(1891±35) pmolAMC/min/mg]和胰蛋白酶活性[(0.358±0.098)pmol/mg比(0.827±0.126)pmol/mg]低于野生型小鼠(P＜0.05),而組織蛋白酶L活性相反[(415±11)pmolAMC/min/mg比(346 ±6) pmolAMC/min/mg] (P＜0.01).結論 P13Kγ在急性胰腺炎時可能具有促進細胞壞死的作用,其可能機製是改變瞭組織蛋白酶B和L之間的平衡和促進瞭胰蛋白酶原的活化.
목적 연구린지선기순3-격매γ(P13Kγ)재실험성급성이선염선포세포배사중적작용,병탐토기작용궤제.방법 12지웅성야생형C57BL/6소서화12지웅성P13Kγ기인고제소서수궤분위대조조화이선염조,복강내분별주사생리염수화와피소(50tμg/kg)유도급성이선염모형.관찰량충동물모형이선조직병리변화,동시검측혈청이단백매활성、조직단백매B화L활성적변화,Western blotting검측조직단백매B화L단백적표체.결과 조직학현시,P13Kγ기인고제소서이선염선포세포배사수량[(2.25±0.54)/HP비(5.14±0.85)/HP]화공포수량[(1.24±0.21)/HP비(2.36±0.34)/HP]명현소우야생형소서(P＜0.05),조직단백매B[(1232±21)pmolAMC/min.mg 비(1891±35) pmolAMC/min/mg]화이단백매활성[(0.358±0.098)pmol/mg비(0.827±0.126)pmol/mg]저우야생형소서(P＜0.05),이조직단백매L활성상반[(415±11)pmolAMC/min/mg비(346 ±6) pmolAMC/min/mg] (P＜0.01).결론 P13Kγ재급성이선염시가능구유촉진세포배사적작용,기가능궤제시개변료조직단백매B화L지간적평형화촉진료이단백매원적활화.
Objective To study the role and mechanism of phosphatidylinositide 3-kinase gamma (P13Kγ) in mediating acinar cell necrosis in rat models with acute pancreatitis.Methods Twelve male C57BL/6 wild-type and twelve male P13Ky knockout mice were randomly divided into saline group and pancreatitis group.The pancreatitis group received an intraperitoneal injection of cerulean (50 μg/kg) to induce acute panreatitis.Pathologic changes in the two groups were observed by measuring the trypsin,cathepsin B,and cathepsin L activity.The protein expressions of cathepsin B and cathepsin L were detected by the Western blot assay.Results Compared with the wild-type mice,the P13Kγγknockout mice had fewer acinar cell necrosis [(2.25± 0.54)/HP vs (5.14±0.85)/HP] and vacuoles [(1.24±0.21)/HP vs (2.36± 0.34)/HP]according to histology.The cathepsin B activity [(1232± 21)pmolAMC/min/mg vs (1891 ±35)pmolAMC/min/mg] and trypsin activity [(0.358± 0.098)pmol/mg vs (0.827± 0.126)pmol/mg] were significantly decreased in the pancreatitis group (P＜0.05) compared to the saline group.However,the cathepsin L activity [ (415 ±11 ) pmolAMC/ min/mg vs (346 ± 6)pmolAMC/min/mg] was significantly higher in P13Kγγ knockout mice than in wild-type mice(P＜0.01).Conclusions P13Kγmay promote cell necrosis in acute pancreatitis by possibly changing the balance between eathepsin B and cathepsin L levels to promote the activation of trypsinogen.
