郑州大学学报（医学版）
鄭州大學學報（醫學版）
정주대학학보（의학판）
JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES)
2015年
4期
496-499
,共4页
丰树焕%张东铭%乐婷%张苏河%付艳芹
豐樹煥%張東銘%樂婷%張囌河%付豔芹
봉수환%장동명%악정%장소하%부염근
大鼠%内质网应激%蛋白激酶R样内质网激酶%C/EBP同源蛋白%β细胞凋亡
大鼠%內質網應激%蛋白激酶R樣內質網激酶%C/EBP同源蛋白%β細胞凋亡
대서%내질망응격%단백격매R양내질망격매%C/EBP동원단백%β세포조망
rat%endoplasmic reticulum stress%PERK%CHOP%β cell apoptosis
目的：：探讨磷酸化蛋白激酶 R 样内质网激酶(p-PERK)、C/ EBP 同源蛋白(CHOP)、ATF4蛋白的表达与高脂高糖诱导的妊娠期糖尿病大鼠胰岛β细胞凋亡的关系。方法：30只雌性 SD 大鼠分为模型组(高脂高糖喂养)和对照组(普食喂养),每组15只,妊娠第21天行静脉糖耐量及静脉胰岛素释放实验；取胰腺组织行 HE 染色和病理组织学观察,TUNEL 法检测胰岛β细胞凋亡情况,免疫组化法检测胰腺组织中 p-PERK 蛋白的表达,Western blot检测胰腺组织中 ATF4及 CHOP 蛋白的表达。结果：模型组大鼠第一时相胰岛素分泌受抑制,胰岛素分泌峰值延迟；病理组织学可见模型组大鼠胰岛形态欠规则,数目减少不明显,部分细胞空泡变性,毛细血管扩张、充血,有出血发生。模型组大鼠胰腺组织细胞凋亡率较对照组升高(t =21.164,P <0.001)。与对照相比,模型组大鼠胰腺组织 p-PERK、ATF4及 CHOP 蛋白表达水平明显升高(t =44.178、49.249、39.664,P <0.001)；模型组大鼠胰腺组织中 ATF4与 CHOP 蛋白的表达呈正相关(r =0.810,P =0.004)。结论：PERK、ATF4可能参与妊娠期糖尿病大鼠胰岛β细胞凋亡的发生。
目的：：探討燐痠化蛋白激酶 R 樣內質網激酶(p-PERK)、C/ EBP 同源蛋白(CHOP)、ATF4蛋白的錶達與高脂高糖誘導的妊娠期糖尿病大鼠胰島β細胞凋亡的關繫。方法：30隻雌性 SD 大鼠分為模型組(高脂高糖餵養)和對照組(普食餵養),每組15隻,妊娠第21天行靜脈糖耐量及靜脈胰島素釋放實驗；取胰腺組織行 HE 染色和病理組織學觀察,TUNEL 法檢測胰島β細胞凋亡情況,免疫組化法檢測胰腺組織中 p-PERK 蛋白的錶達,Western blot檢測胰腺組織中 ATF4及 CHOP 蛋白的錶達。結果：模型組大鼠第一時相胰島素分泌受抑製,胰島素分泌峰值延遲；病理組織學可見模型組大鼠胰島形態欠規則,數目減少不明顯,部分細胞空泡變性,毛細血管擴張、充血,有齣血髮生。模型組大鼠胰腺組織細胞凋亡率較對照組升高(t =21.164,P <0.001)。與對照相比,模型組大鼠胰腺組織 p-PERK、ATF4及 CHOP 蛋白錶達水平明顯升高(t =44.178、49.249、39.664,P <0.001)；模型組大鼠胰腺組織中 ATF4與 CHOP 蛋白的錶達呈正相關(r =0.810,P =0.004)。結論：PERK、ATF4可能參與妊娠期糖尿病大鼠胰島β細胞凋亡的髮生。
목적：：탐토린산화단백격매 R 양내질망격매(p-PERK)、C/ EBP 동원단백(CHOP)、ATF4단백적표체여고지고당유도적임신기당뇨병대서이도β세포조망적관계。방법：30지자성 SD 대서분위모형조(고지고당위양)화대조조(보식위양),매조15지,임신제21천행정맥당내량급정맥이도소석방실험；취이선조직행 HE 염색화병리조직학관찰,TUNEL 법검측이도β세포조망정황,면역조화법검측이선조직중 p-PERK 단백적표체,Western blot검측이선조직중 ATF4급 CHOP 단백적표체。결과：모형조대서제일시상이도소분비수억제,이도소분비봉치연지；병리조직학가견모형조대서이도형태흠규칙,수목감소불명현,부분세포공포변성,모세혈관확장、충혈,유출혈발생。모형조대서이선조직세포조망솔교대조조승고(t =21.164,P <0.001)。여대조상비,모형조대서이선조직 p-PERK、ATF4급 CHOP 단백표체수평명현승고(t =44.178、49.249、39.664,P <0.001)；모형조대서이선조직중 ATF4여 CHOP 단백적표체정정상관(r =0.810,P =0.004)。결론：PERK、ATF4가능삼여임신기당뇨병대서이도β세포조망적발생。
Aim: To investigate the relationship between the activation of p-PERK,ATF4 and CHOP protein and isletβ cell apoptosis of pregnant rats with high sucrose and fat diet. Methods: Thirty healthy female SD rats were allocated into two groups randomly: control group(n = 15) and gestational diabetes mellitus(GDM) model group(n = 15). Twenty-one days after gestation,intravenous glucose tolerance test(IVGTT) and intravenous insulin releasing test(IVIRT) were per-formed;the pancreas was removed for examination of morphological and ultra structural changes; the islet β cell apoptosis index was calculated by TUNEL;the expression of p-PERK in pancreatic tissue was analyzed by immunohistochemistry;the expressions of ATF4 and CHOP protein were analyzed by Western blot. Results: The first-phase insulin secretion of rats in the GDM model group was inhibited,and the insulin secretion peak was delayed;the islet morphology was not regular,the reducing was not obvious,some cells degenerated,blood capillaries dilated,and there was hyperemia or bleeding occurred in the GDM model group by means of HE staining;the apoptotic rate increased in the GDM model group(t = 21. 164,P <0. 001);compared with control group,the level of p-PERK,ATF4,and CHOP in pancreatic tissue increased significantly in the GDM model group(t = 44. 178,49. 249,and 39. 664,P < 0. 05). Correlation analysis showed that the expression level of ATF4 was positively correlated with CHOP protein in islet tissue from rats in the GDM model group( r = 0. 810,P =0. 004). Conclusion: The activation expressions of ATF4 and PERK protein may participate in apoptosis of pancreatic βcells in GDM rats induced by high sucrose and fat diet.
