Matsushita Koki, Mizushima Takaaki, Shirahige Akinori, Tanioka Hiroaki, Sawa Kiminari, Ochi Koji, Tanimoto Mitsune, Koide Norio
Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Acta Med Okayama. 2012;66(4):329-34. doi: 10.18926/AMO/48687.
The relationship between pancreatic fibrosis and apoptosis of pancreatic acinar cells has not been fully elucidated. We reported that taurine had an anti-fibrotic effect in a dibutyltin dichloride (DBTC)-chronic pancreatitis model. However, the effect of taurine on apoptosis of pancreatic acinar cells is still unclear. Therefore, we examined apoptosis in DBTC-chronic pancreatitis and in the AR42J pancreatic acinar cell line with/without taurine. Pancreatic fibrosis was induced by a single administration of DBTC. Rats were fed a taurine-containing diet or a normal diet and were sacrificed at day 5. The AR42J pancreatic acinar cell line was incubated with/without DBTC with taurine chloramines. Apoptosis was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. The expression of Bad and Bcl-2 proteins in the AR42J cells lysates was detected by Western blot analysis. The apoptotic index of pancreatic acinar cells in DBTC-administered rats was significantly increased. Taurine treatment inhibited pancreatic fibrosis and apoptosis of acinar cells induced by DBTC. The number of TUNEL-positive cells in the AR42J pancreatic acinar cell lines was significantly increased by the addition of DBTC. Incubation with taurine chloramines ameliorated these changes. In conclusion, taurine inhibits apoptosis of pancreatic acinar cells and pancreatitis in experimental chronic pancreatitis.
胰腺纤维化与胰腺腺泡细胞凋亡之间的关系尚未完全阐明。我们曾报道，在二丁基二氯化锡（DBTC）诱导的慢性胰腺炎模型中，牛磺酸具有抗纤维化作用。然而，牛磺酸对胰腺腺泡细胞凋亡的影响仍不清楚。因此，我们检测了在有/无牛磺酸情况下，DBTC诱导的慢性胰腺炎及AR42J胰腺腺泡细胞系中的细胞凋亡情况。通过单次给予DBTC诱导胰腺纤维化。给大鼠喂食含牛磺酸的饮食或正常饮食，并在第5天处死。将AR42J胰腺腺泡细胞系与含/不含DBTC及氯胺牛磺酸一起孵育。采用末端脱氧核苷酸转移酶介导的dUTP-地高辛缺口末端标记（TUNEL）法测定细胞凋亡。通过蛋白质免疫印迹分析检测AR42J细胞裂解物中Bad和Bcl-2蛋白的表达。给予DBTC的大鼠胰腺腺泡细胞凋亡指数显著增加。牛磺酸治疗可抑制DBTC诱导的胰腺纤维化及腺泡细胞凋亡。加入DBTC后，AR42J胰腺腺泡细胞系中TUNEL阳性细胞数量显著增加。与氯胺牛磺酸一起孵育可改善这些变化。总之，在实验性慢性胰腺炎中，牛磺酸可抑制胰腺腺泡细胞凋亡及胰腺炎。
