CAJ | 학술논문

目的观察渥曼青霉素(wortmannin)对急性胰腺炎并发肾功能损伤的治疗作用,探讨wortmannin对磷酸肌醇3激酶(PI3K)/蛋白激酶B(PKB)信号转导通路的影响.方法 80只健康清洁级SD雄性大鼠,随机分为正常对照组、假手术组(SO组)、急性胰腺炎组(AP组)和wortmannin 组,其中SO组、AP组和wortmannin组再分为3、6、12 h亚组,每组8只.胆胰管内逆行注射法制作AP模型,wortmannin组术前4h腹腔注射wortmannin.取外周血、肾脏和胰腺,分别检测血清尿素氮、肌酐、淀粉酶、肾脏和胰腺病理学检查和肾脏和胰腺中PKB、p-PKB和肿瘤坏死因子-α(TNF-α)蛋白检查.结果 AP组和wortmannin组术后3h大鼠肾脏和胰腺病理损伤程度、外周血清中尿素氮[(9.81 ±1.28)、(77.49±1.17)比(5.33 ±0.32) mmol/L]、肌酐[(62.19±5.84)、(55.12 ±5.27)比(45.13 ±3.01) μmol/L]、淀粉酶水平水平[(2931 ±619)、(2061 ±897)比(677±120) U/L]显著高于SO组(P＜0.05),且术后6h和12h差异更加明显;术后12 h wortmannin组肾脏和胰腺病理损伤程度、外周血清中尿素氮[(16.51±2.00)比(21.16±2.57) mmol/L]、肌酐[(94.63±11.30)比(116.24±14.82) μmol/L]、淀粉酶水平[(3 264±932)比(7725±1 517) U/L]、肾脏和胰腺中p-PKB(1.01 ±0.24比1.23±0.30)和TNF-α(1.11 ±0.29比1.33±0.37)蛋白表达水平显著低于AP组(P＜0.05).结论 PI3K/PKB信号转导通路的激活在急性胰腺炎并发肾功能损伤的发生和发展的过程中起着非常重要的作用,采用PI3K抑制剂wortmannin可以显著改善急性胰腺炎并发肾功能的损伤.
목적 관찰악만청매소(wortmannin)대급성이선염병발신공능손상적치료작용,탐토wortmannin대린산기순3격매(PI3K)/단백격매B(PKB)신호전도통로적영향.방법 80지건강청길급SD웅성대서,수궤분위정상대조조、가수술조(SO조)、급성이선염조(AP조)화wortmannin 조,기중SO조、AP조화wortmannin조재분위3、6、12 h아조,매조8지.담이관내역행주사법제작AP모형,wortmannin조술전4h복강주사wortmannin.취외주혈、신장화이선,분별검측혈청뇨소담、기항、정분매、신장화이선병이학검사화신장화이선중PKB、p-PKB화종류배사인자-α(TNF-α)단백검사.결과 AP조화wortmannin조술후3h대서신장화이선병리손상정도、외주혈청중뇨소담[(9.81 ±1.28)、(77.49±1.17)비(5.33 ±0.32) mmol/L]、기항[(62.19±5.84)、(55.12 ±5.27)비(45.13 ±3.01) μmol/L]、정분매수평수평[(2931 ±619)、(2061 ±897)비(677±120) U/L]현저고우SO조(P＜0.05),차술후6h화12h차이경가명현;술후12 h wortmannin조신장화이선병리손상정도、외주혈청중뇨소담[(16.51±2.00)비(21.16±2.57) mmol/L]、기항[(94.63±11.30)비(116.24±14.82) μmol/L]、정분매수평[(3 264±932)비(7725±1 517) U/L]、신장화이선중p-PKB(1.01 ±0.24비1.23±0.30)화TNF-α(1.11 ±0.29비1.33±0.37)단백표체수평현저저우AP조(P＜0.05).결론 PI3K/PKB신호전도통로적격활재급성이선염병발신공능손상적발생화발전적과정중기착비상중요적작용,채용PI3K억제제wortmannin가이현저개선급성이선염병발신공능적손상.
Objective To explore the therapeutic effect of wortmannin on acute pancreatitis (AP) with renal dysfunction and on phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB) signaling pathway.Methods Eighty healthy male SD rats were randomly divided into normal control group,sham operation group (SO group),AP group and wortmannin group.SO group,AP group and wortmannin group were further divided into 3,6 and 12 h sub-groups (n =8 each).The AP model was established by bile duct retrograde injection.Wortmannin was intraperitoneally injected 4 h before operation.Serum urea nitrogen,creatinine,amylase,pathological findings of the kidney and pancreas,and PKB,p-PKB and tumor necrosis factor-α (TNF-α) proteins in the kidney and pancreas were observed.Results Histopathological damage of the kidney and pancreas was severer,blood urea nitrogen [(9.81 ± 1.28) and (77.49±1.17) vs.(5.33 ±0.32) mmol/L],creatinine [(62.19 ±5.84) and (55.12 ±5.27) vs.(45.13 ±3.01) μmol/L] and amylase levels [(2 931 ±619) and (2 061 ±897) vs.(677 ± 120) U/L] were significantly higher in AP group and wortmannin group than in SO group 3 h after operation (P ＜ 0.05),more significantly in 6 h and 12 h sub-groups.Histopathological damage of the kidney and pancreas was severed,blood urea nitrogen [(16.51 ± 2.00) vs.(21.16 ± 2.57) mmol/L],creatinine [(94.63±11.30) vs.(116.24± 14.82) μmol/L],amylase levels [(3264±932) vs.(7725± 1 517) U/L],p-PKB (1.01 ± 0.24 vs.1.23±0.30) andTNF-αproteins (1.11±0.29vs.1.33± 0.37) levels were significantly lower in wortmannin group than in AP group at 12 h after operation (P ＜ 0.05).Conclusion Activation of PI3K/PKB signaling pathway plays a very important role in the occurrence and development of AP with renal function dysfunction.PI3K inhibitors (wortmannin) can significantly alleviate the renal function damage induced by AP.