Mechanisms of Chinese herb emodin and somatostatin analogs on pancreatic regeneration in acute pancreatitis in rats.
BACKGROUND
Studies have revealed that emodin is a potent agent in the management of clinical and experimental acute pancreatitis, but the molecular mechanisms by which emodin produces its biologic effects, especially on pancreatic regeneration after acute pancreatitis, remain unknown. Numerous experimental and clinical studies have shown that somatostatin analogs have favorable effects on acute pancreatitis, but their role in the management of acute pancreatitis remains controversial.


OBJECTIVE
To investigate mechanisms of the Chinese herb emodin and somatostatin analogs (SSa; Sandostatin) in acute pancreatitis of rats by analyzing the changes in pancreatic tissue cytokine transforming growth factor beta1 (TGFbeta1) and epidermal growth factor (EGF) gene expression, DNA synthesis, total protein content, and the relations between them.


METHODS
Acute pancreatitis was induced by intraperitoneal infusion of cerulein in rats. Emodin was administered intravenously and Sandostatin was administered subcutaneously at the time of induction of pancreatitis and 24, 48, and 72 hours afterward. Rats were killed at 6, 24, 48, 72, and 96 hours after the operation. The mRNA expression of TGFbeta1 and EGF were evaluated by reverse transcription polymerase chain reaction, and pancreatic tissue DNA synthesis was measured by the 3H-thymidine incorporation method in vitro. Total protein content was detected by Lowry's method.


RESULTS
The serum amylase level was decreased significantly in the emodin-treated and Sandostatin-treated groups in comparison with the nontreated group. Pancreatic tissue DNA synthesis was significantly decreased at 72 hours after the induction of pancreatitis, and a marked increase was observed at 96 hours after treatment with emodin and Sandostatin. Within 48 hours of the induction of pancreatitis, the total protein content in pancreatic tissue declined, but there was a remarkable increase in the emodin-treated group at 96 hours and Sandostatin-treated group at 48 hours. Expression of TGFbeta1 mRNA and EGF mRNA were undetectable in normal pancreas and the nontreated group at 6 hours but was observed from 24 hours to 96 hours after the induction of pancreatitis and reached its maximum at 72 hours. TGFbeta1 mRNA could be detected 6 hours after treatment with emodin and Sandostatin, and its expression was significantly higher in the emodin-treated and Sandostatin-treated groups than in the nontreated group at 24 and 48 hours. The expression of EGF mRNA was significantly higher in the emodin-treated and Sandostatin-treated group than in the nontreated group at 48 hours.


CONCLUSIONS
It was concluded that mechanisms of the Chinese herb emodin and somatostatin analogs in the management of acute pancreatitis in rats might be ascribed to the upregulation of TGFbeta1 and EGF gene expression, which subsequently increases DNA synthesis and protein content and thus accelerates pancreatic repair and regeneration.
Gong
Zihua
Z
Department of Gastroenterology, Shanghai First People's Hospital, Shanghai Second Medical University, Shanghai, China.
Yuan
Yaozog
Y
Lou
Kaixian
K
Tu
Shuiping
S
Zhai
Zukang
Z
Xu
Jiayu
J
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000187:drug effects; D000818:Animals; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D004642:Emodin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D010195:Pancreatitis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D006728:Hormones; D011506:Proteins; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D004247:DNA; D000681:Amylases; D004642:Emodin; D015282:Octreotide