中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2015年
5期
400-405
,共6页
AT1受体自身抗体%厄贝沙坦%内质网应激%凋亡%糖尿病肾病
AT1受體自身抗體%阨貝沙坦%內質網應激%凋亡%糖尿病腎病
AT1수체자신항체%액패사탄%내질망응격%조망%당뇨병신병
AT1 receptor autoantibody%Irbesartan%Endoplasmic reticulum stress%Apoptosis%Diabetic nephropathy
目的 探讨血管紧张素Ⅱ1型受体自身抗体(AT1-AA)对厄贝沙坦(Irbesartan,Irb)抑制糖尿病肾脏病(DN)大鼠肾脏内质网应激(ERS)相关凋亡信号通路的影响.方法 建立DN模型大鼠,ELISA法检测成模DN大鼠血清AT1-AA.将AT1-AA阳性和阴性DN大鼠分到DN组和Irb干预组中,并设正常对照(NC)组.Irb干预4周,观察肾脏超微结构变化,TUNEL法检测肾脏细胞凋亡,Western印迹和RTPCR技术测定肾脏ERS标志蛋白葡萄糖调节蛋白78(GRP78)及凋亡蛋白CCAAT/增强子结合蛋白同源蛋白(CHOP)、磷酸化的c-Jun氨基末端激酶(p-JNK)和半胱氨酸天冬氨酸蛋白酶12(Caspase12)蛋白及mRNA水平.结果 DN组大鼠肾脏细胞凋亡较NC组显著增加,其GRP78、CHOP、p-JNK和Caspase12蛋白及mRNA表达也显著增加,Irb干预后明显降低(均P＜0.01),在AT1-AA阳性大鼠较阴性大鼠降低尤为显著(均P＜0.05).DN组AT1-AA阳性大鼠细胞凋亡率及这4个基因的蛋白和mRNA水平均高于AT1-AA阴性大鼠(均P＜0.05).结论 AT1-AA可能与DN大鼠肾脏ERS介导的肾脏细胞凋亡有关,并在Irb抑制ERS相关的CHOP-JNK-Caspase12凋亡信号、减少细胞凋亡、保护肾脏功能中起作用.
目的 探討血管緊張素Ⅱ1型受體自身抗體(AT1-AA)對阨貝沙坦(Irbesartan,Irb)抑製糖尿病腎髒病(DN)大鼠腎髒內質網應激(ERS)相關凋亡信號通路的影響.方法 建立DN模型大鼠,ELISA法檢測成模DN大鼠血清AT1-AA.將AT1-AA暘性和陰性DN大鼠分到DN組和Irb榦預組中,併設正常對照(NC)組.Irb榦預4週,觀察腎髒超微結構變化,TUNEL法檢測腎髒細胞凋亡,Western印跡和RTPCR技術測定腎髒ERS標誌蛋白葡萄糖調節蛋白78(GRP78)及凋亡蛋白CCAAT/增彊子結閤蛋白同源蛋白(CHOP)、燐痠化的c-Jun氨基末耑激酶(p-JNK)和半胱氨痠天鼕氨痠蛋白酶12(Caspase12)蛋白及mRNA水平.結果 DN組大鼠腎髒細胞凋亡較NC組顯著增加,其GRP78、CHOP、p-JNK和Caspase12蛋白及mRNA錶達也顯著增加,Irb榦預後明顯降低(均P＜0.01),在AT1-AA暘性大鼠較陰性大鼠降低尤為顯著(均P＜0.05).DN組AT1-AA暘性大鼠細胞凋亡率及這4箇基因的蛋白和mRNA水平均高于AT1-AA陰性大鼠(均P＜0.05).結論 AT1-AA可能與DN大鼠腎髒ERS介導的腎髒細胞凋亡有關,併在Irb抑製ERS相關的CHOP-JNK-Caspase12凋亡信號、減少細胞凋亡、保護腎髒功能中起作用.
목적 탐토혈관긴장소Ⅱ1형수체자신항체(AT1-AA)대액패사탄(Irbesartan,Irb)억제당뇨병신장병(DN)대서신장내질망응격(ERS)상관조망신호통로적영향.방법 건립DN모형대서,ELISA법검측성모DN대서혈청AT1-AA.장AT1-AA양성화음성DN대서분도DN조화Irb간예조중,병설정상대조(NC)조.Irb간예4주,관찰신장초미결구변화,TUNEL법검측신장세포조망,Western인적화RTPCR기술측정신장ERS표지단백포도당조절단백78(GRP78)급조망단백CCAAT/증강자결합단백동원단백(CHOP)、린산화적c-Jun안기말단격매(p-JNK)화반광안산천동안산단백매12(Caspase12)단백급mRNA수평.결과 DN조대서신장세포조망교NC조현저증가,기GRP78、CHOP、p-JNK화Caspase12단백급mRNA표체야현저증가,Irb간예후명현강저(균P＜0.01),재AT1-AA양성대서교음성대서강저우위현저(균P＜0.05).DN조AT1-AA양성대서세포조망솔급저4개기인적단백화mRNA수평균고우AT1-AA음성대서(균P＜0.05).결론 AT1-AA가능여DN대서신장ERS개도적신장세포조망유관,병재Irb억제ERS상관적CHOP-JNK-Caspase12조망신호、감소세포조망、보호신장공능중기작용.
Objective To investigate the role of AT1 receptor autoantibody (AT1-AA) in the inhibitory action of irbesartan on endoplasmic reticulum stress (ERS)-related apoptotic signals in rat kidney with diabetic nephropathy (DN).Methods DN model rats were induced by high-sugar and high-fat diet plus intraperitoneal injection of streptozotocin,and the serum level of AT1-AA was detected by ELISA.These DN rats with positive or negative AT1-AA were divided into DN group and irbesartan treated group.After 4 weeks of irbesartan treatment,TUNEL staining was used to detect renal cell apoptosis.The protein and mRNA expressions of ERS chaperone protein glucose-regulated protein 78 (GRP78) and ERS-associated apoptosis proteins were determined by Western blot and RT-PCR.Results Compared with NC group,the apoptosis rate of renal cells in DN group was obviously increased,along with the increased expressions of GRP78,C/EBP homology protein (CHOP),phosphorylated c-Jun N-terminal kinase (JNK),and Caspase12 protein and mRNA (all P＜0.01).The cell apoptosis and protein and mRNA levels of these genes were significantly decreased after irbesartan treatment (all P＜ 0.01),especially in AT1-AA positive DN rats(all P＜0.05).The renal cell apoptosis rate,and protein and mRNA levels of these four genes in AT1-AA positive DN group were much greater than those in AT1-AA negative DN group (all P＜0.05).Conclusions AT1-AA may be involved in ERS-related cell apoptosis in the kidney of DN rats,and play a role in irbesartan-improved renal function via inhibiting ERS-associated CHOP-JNK-Caspase12 apoptotic signals and renal cell apoptosis.
