摘要
目的 探讨洛沙坦对TNBS诱导大鼠实验性胰腺纤维化形成过程中胰腺腺泡细胞凋亡的影响及可能机制。方法 雄性SD大鼠 10 0只随机分为正常组、对照组、治疗组 ,采用胰管内注射 2 %三硝基苯磺酸 (TNBS)诱导大鼠胰腺纤维化模型。治疗组每天给予洛沙坦 (10mg/kg)灌胃 ;对照组给予等容积的无菌蒸馏水。观察胰腺组织病理改变 ;TUNEL法原位检测凋亡胰腺腺泡细胞密度 ;透射电镜观察胰腺组织细胞形态学变化 ;逆转录 -多聚酶链反应 (RT PCR)方法检测Bcl 2凋亡相关基因家族成员Bcl 2、Bcl XL、Bak、BaxmRNA表达。结果 洛沙坦治疗可逆转胰腺组织炎症细胞浸润、腺泡萎缩等异常改变。对照组大鼠胰腺腺泡细胞凋亡较正常大鼠明显增加 ,胰腺组织Bax、BakmRNA表达较正常增加 ,Bcl 2mRNA表达降低 ,Bcl XLmRNA不表达 ;洛沙坦治疗后凋亡减少 ,洛沙坦治疗组Bax、Bcl 2mRNA表达及Bax/Bcl 2较对照组降低 ,Bak、Bcl XLmRNA不表达。结论 TNBS诱导大鼠胰腺纤维化形成过程中胰腺腺泡细胞凋亡增加 ;洛沙坦阻断 1型血管紧张素Ⅱ受体 (AT1R)可抑制其凋亡 ,其机制可能与调控bcl 2凋亡相关基因表达有关。由此可见 。
Purpose To investigate the effects and the possible mechanism of losartan on apoptosis of pancreatic acinar cells in rat pancreatic fibrosis induced by trinitrobenenze sulfonic acid (TNBS). Methods Male Sprague-Dawley rats (200-300 g) were randomly divided into normal group, control group and losartan-treatment group. Pancreatic fibrosis was induced by infusion of 2% TNBS into the pancreatic duct. Rats in losartan-treatment group and control group were respectively treated with losartan(10 mg/kg)by gavage daily and the same volume of sterile distilled water. The histological abnormalities were observed by HE staining and the morphology of pancreatic acinar cells apoptosis by electron microscope. The density of apopyosis cells was assessed by the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL). The expression of Bax, Bak, Bcl-2 and Bcl-XL, members of the Bcl-2 family of apoptosis-associated genes , were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results Losartan treatment reversed the histological abnormalities including infiltration of inflammatory cells and acinar cells atrophy. Compared with normal rats, untreated pancreatic fibrosis rats exhibited increased apopyosis, increased Bax,Bak mRNA and decreased Bcl-2 mRNA. The administration of Losartan resulted in inhibiting acinar cells apoptosis and down-regulating expressions of Bax,Bak,Bcl-2 mRNA. The expression of Bcl-XL could be hardly detected in all rats. The Bax/Bcl-2 ratio was higher in control rats than that in treated rats. Conclusions Losartan prevents apoptosis of pancreatic acinar cells by blocking angiotensin Ⅱ type 1 receptors (AT 1R)during the development of pancreatic fibrosis induced by 2% TNBS, which might be associated with regulating the expressions of the Bcl-2 family of apoptosis-associated genes. According the results, it can be proposed that the interaction of angiotensin Ⅱ with its AT 1R may participate in the pancreatic acinar cells apoptosis.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2004年第2期158-161,F003,共5页
Fudan University Journal of Medical Sciences
基金
上海市科技发展基金 ( 0 14 1190 65 )资助项目
