Apoptosis of Pancreas Acinar Cell Induced by Artemisinin in Acute Pancreatitis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Weihui ¹ , ZHENG Biao ¹ , XUE Dongbo ¹ , PAN Shangha ² , SHI Xingye ¹ , SUN Bei ¹

Department of General Surgery, The First Clinical College of Harbin Medical University, Harbin 150001, China;

Corresponding author：

Keywords：

Pancreatitis; Artemisinin; Pancreas acinar cell; Apoptosis

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Objective 　To explore the effect of artemisinin on the apoptosis of pancreas acinar cells in acute pancreatitis (AP), and to study whether artemisinin can relieve the severity of AP.
Methods 　① In vivo experiment: twenty one Wistar rats were divided into the following 3 groups randomly: the normal control group, the AP group and the artemisinin group. The model of AP was established by injecting cerulein into the peritoneal cavity of rat. After establishment of AP in the artemisinin group, artemisinin was injected into the peritoneal cavity. Meanwhile normal saline was injected into the peritoneal cavity of rats of the normal control group and the AP group. The apoptosis of pancreas acinar cell was detected by terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL). The activity of myeloperoxidase was detected by absorption spectrometry. ② In vitro experiment: the pancreas acinar cells of normal rats were isolated through twostep enzyme digestion, and cultured. These acinar cells were divided into 3 groups: the normal control group, the AP group and the artemisinin group. Then, the cells of AP group were cocultured with cerulein, and those of the artemisinin group were cocultured with cerulein and artemisinin. The apoptosis of pancreas acinar cells were detected by AO dyeing and the measurement of the activity of caspase3. And the activity of LDH and AMS in the culture medium of each group were measured.
Results 　① In vivo: the apoptosis index of the artemisinin group was sigificantly increased and the activity of myeloperoxidase was obviously decreased compared with the AP group (P＜0.05). ② In vitro: the apoptosis index and the activity of caspase3 of the artemisinin group were significantly increased compared with the AP group (P＜0.05);　 the activities of LDH and AMS of the artemisinin group were more decreased than those of the AP group (P＜0.05).　
Conclusion 　Artemisinin could contribute to the apoptosis of rat pancreas acinar cells, decrease the releasing of trypsogen, alleviate the activation of neutrophil and relieve the severity of AP.

Citation： ZHANG Weihui,ZHENG Biao,XUE Dongbo,PAN Shangha,SHI Xingye,SUN Bei. Apoptosis of Pancreas Acinar Cell Induced by Artemisinin in Acute Pancreatitis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 388-391. doi: Copy

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6.	Kaiser AM, Saluja AK, Sengupta A, et al. Relationship between severity, necrosis, and apoptosis in five models of experimental acute pancreatitis[J]. Am J Physiol, 1995; 269(5 Pt 1)　∶C1295.
7.	常华, 严际慎, 王平瑜, 等. 缺血再灌注损伤对大鼠急性胰腺炎胰腺细胞凋亡的影响 [J]. 中国普外基础与临床杂志, 2005; 12(2)∶150.
8.	陈晓理, 黄兴兰, 吴浩. 急性胰腺炎血中抗炎症细胞因子的意义[J]. 中国普外基础与临床杂志, 2000; 7(6)∶354.
9.	杨智勇, 王春友, 陶京, 等. 早期血液滤过对重症急性胰腺炎家猪TNFα及IL1β水平的影响[J]. 中国普外基础与临床杂志, 2004; 11(5)∶433.
10.	高军，张淑文，李非. 胰蛋白酶原激活肽在大鼠实验性急性胰腺炎中的产生及意义[J]. 中国普外基础与临床杂志, 2001； 8(5)∶301.
11.	Rinderknecht H. Fatal pancreatitis, a consequence of excessive leukocyte stimulation? [J]. Int J Pancreatol， 1988; 3(2-3)∶105.
12.	Chiu DF, Chen JC, Chen HM, et al. Results of treating severe acute pancreatitis with gabexate is associated with neutrophil apoptosis activity[J]. Hepatogastroenterology， 2003; 50(50)∶553.
13.	Yamaguchi Y, Okabe K, Liang J, et al. The novel carboxamide derivative IS741 reduces neutrophil chemoattractant production by bronchoalveolar macrophages in rats with ceruleininduced pancreatitis complicated by sepsis[J]. Digestion， 1999; 60 Suppl 1∶52.
14.	Hahm KB, Kim JH, You BM, et al. Induction of apoptosis with an extract of Artemisia asiatica attenuates the severity of ceruleininduced pancreatitis in rats[J]. Pancreas， 1998; 17(2)∶153.
15.	Gallagher SF, Yang J , Bak sh K, et al. Acute pancreatitis induces FasL gene expression and apoptosis in the liver[J]. J Surg Res, 2004； 122(2)∶201.

1. 　He ZJ, Podkletnova I, Alho H, et al. Apoptosis in acute pancreatitis[J]. Ann Chir Gynaecol, 2000; 89(1)∶65.
2. 　李涛，罗军，温浩. 细胞凋亡在大鼠胰腺移植急性排斥反应中的作用 [J]. 中国普外基础与临床杂志， 2007; 14（1）∶59.
3. 　Singh NP, Lai HC. Artemisinin induces apoptosis in human cancer cells[J]. Anticancer Res, 2004; 24(4)∶2277.
4. 　李全生，陈晓理，周总光，等. 雨蛙素腹腔注射法建立小鼠急性坏死性胰腺炎模型的实验研究 [J]. 中国普外基础与临床杂志, 2004; 11(4)∶335.
5. 　Moinfar F, Mannion C, Man YG, et al. Mammary “comedo”DCIS: apoptosis, oncosis, and necrosis: an electron microscopic examination of 8 cases[J]. Ultrastruct Pathol, 2000; 24(3)∶135.
6. 　Kaiser AM, Saluja AK, Sengupta A, et al. Relationship between severity, necrosis, and apoptosis in five models of experimental acute pancreatitis[J]. Am J Physiol, 1995; 269(5 Pt 1)　∶C1295.
7. 　常华, 严际慎, 王平瑜, 等. 缺血再灌注损伤对大鼠急性胰腺炎胰腺细胞凋亡的影响 [J]. 中国普外基础与临床杂志, 2005; 12(2)∶150.
8. 　陈晓理, 黄兴兰, 吴浩. 急性胰腺炎血中抗炎症细胞因子的意义[J]. 中国普外基础与临床杂志, 2000; 7(6)∶354.
9. 　杨智勇, 王春友, 陶京, 等. 早期血液滤过对重症急性胰腺炎家猪TNFα及IL1β水平的影响[J]. 中国普外基础与临床杂志, 2004; 11(5)∶433.
10. 　高军，张淑文，李非. 胰蛋白酶原激活肽在大鼠实验性急性胰腺炎中的产生及意义[J]. 中国普外基础与临床杂志, 2001； 8(5)∶301.
11. 　Rinderknecht H. Fatal pancreatitis, a consequence of excessive leukocyte stimulation? [J]. Int J Pancreatol， 1988; 3(2-3)∶105.
12. 　Chiu DF, Chen JC, Chen HM, et al. Results of treating severe acute pancreatitis with gabexate is associated with neutrophil apoptosis activity[J]. Hepatogastroenterology， 2003; 50(50)∶553.
13. 　Yamaguchi Y, Okabe K, Liang J, et al. The novel carboxamide derivative IS741 reduces neutrophil chemoattractant production by bronchoalveolar macrophages in rats with ceruleininduced pancreatitis complicated by sepsis[J]. Digestion， 1999; 60 Suppl 1∶52.
14. 　Hahm KB, Kim JH, You BM, et al. Induction of apoptosis with an extract of Artemisia asiatica attenuates the severity of ceruleininduced pancreatitis in rats[J]. Pancreas， 1998; 17(2)∶153.
15. 　Gallagher SF, Yang J , Bak sh K, et al. Acute pancreatitis induces FasL gene expression and apoptosis in the liver[J]. J Surg Res, 2004； 122(2)∶201.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Apoptosis of Pancreas Acinar Cell Induced by Artemisinin in Acute Pancreatitis

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