Hahm K B, Kim J H, You B M, Kim Y S, Cho S W, Yim H, Ahn B O, Kim W B
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Pancreas. 1998 Aug;17(2):153-7. doi: 10.1097/00006676-199808000-00007.
The aim of this study was to test the hypothesis that apoptosis can protect against experimental pancreatitis and induction of apoptosis by an extract of Artemisia asiatica (DA-9601) is beneficial in cerulein-induced pancreatis in rats. Pancreatitis was induced in 6-week-old male SPF Sprague-Dawley rats by two intravenous (i.v.) administrations of 40 microg/kg cerulein. To investigate the effects of DA-9601 on the severity of pancreatitis and extent of apoptosis, rats were treated with intragastric DA-9601, 30 mg/kg (D30), 100 mg/kg (D100), or 300 mg/kg (D300), intraperitoneal superoxide dismutase, 10,000 U/kg (SOD), and i.v. gabexate mesilate, 40 mg/kg (Foy), three times (30 min before cerulein injection, 30 and 90 min after cerulein injection). The control group was administered vehicle alone. Ten rats were included in each treatment group and control group. Rats were sacrificed 5 h after cerulein treatment. Serum amylase, histological activity index (HAI), pancreatic lipid peroxide levels, and apoptotic index [in situ hybridization by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL)] were determined. Gel electrophoresis was performed for the presence of DNA fragmentations. The results were as follows. Serum amylase was significantly increased in all cerulein-treated groups compared to normal controls (p < 0.001). The HAI was significantly decreased in only the D300 group compared to the controls (p < 0.05). The apoptotic index of the cerulein-alone group was 3.8 +/- 2.7, but the mean apoptotic indexes of the SOD and Foy groups were 16.4 +/- 4.6 and 13.3 +/- 1.8, respectively, a significant increase (p < 0.01). The apoptotic index was more significantly increased in the DA-9601-treated groups, dose dependently (8.4 +/- 3.4 in D30, 14.8 +/- 4.3 in D100, 24.2 +/- 4.7 in D300). A smearing pattern of DNA electrophoresis was noted in the DA-9601-treated groups. In conclusion, DA-9601, an extract of Artemisia, induced apoptosis of pancreatic acinar cells dose dependently and concomitantly attenuated the severity of pancreatitis.
细胞凋亡可预防实验性胰腺炎，而亚洲龙蒿提取物（DA - 9601）诱导的细胞凋亡对大鼠雨蛙肽诱导的胰腺炎有益。通过两次静脉注射40微克/千克雨蛙肽，诱导6周龄雄性无特定病原体（SPF）斯普拉格 - 道利大鼠发生胰腺炎。为研究DA - 9601对胰腺炎严重程度和细胞凋亡程度的影响，大鼠分别接受胃内给予30毫克/千克（D30）、100毫克/千克（D100）或300毫克/千克（D300）的DA - 9601、腹腔注射10000单位/千克的超氧化物歧化酶（SOD）以及静脉注射40毫克/千克的甲磺酸加贝酯（Foy），均给药三次（在注射雨蛙肽前30分钟、注射雨蛙肽后30分钟和90分钟）。对照组仅给予溶剂。每个治疗组和对照组均纳入10只大鼠。在雨蛙肽处理5小时后处死大鼠。测定血清淀粉酶、组织学活性指数（HAI）、胰腺脂质过氧化物水平以及凋亡指数[通过末端脱氧核苷酸转移酶介导的dUTP - 生物素缺口末端标记法（TUNEL）进行原位杂交]。进行凝胶电泳检测DNA片段化情况。结果如下。与正常对照组相比，所有雨蛙肽处理组的血清淀粉酶均显著升高（p < 0.001）。与对照组相比，仅D300组的HAI显著降低（p < 0.05）。单独雨蛙肽组的凋亡指数为3.8±2.7，但SOD组和Foy组的平均凋亡指数分别为16.4±4.6和13.3±1.8，显著升高（p < 0.01）。在DA - 9601处理组中，凋亡指数升高更显著，呈剂量依赖性（D30组为8.4±3.4，D100组为14.8±4.3，D300组为24.2±4.7）。在DA - 9601处理组中观察到DNA电泳呈拖尾模式。总之，亚洲龙蒿提取物DA - 9601可剂量依赖性地诱导胰腺腺泡细胞凋亡，并同时减轻胰腺炎的严重程度。
