A team led by Professor Qing Xia at the West China Hospital of Sichuan University has determined the genetic treatment mechanism of Chaiqinchengqi decoction, which is a basic Chinese herbal compound commonly used in the treatment of acute pancreatitis. It can upregulate sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) mRNA expression of pancreatic tissue as well as inhibit the elevation of calcium concentration in pancreatic acinar cells while relieving pancreatic lesions in an acute pancreatitis model of rats.
In previous studies, Chaiqinchengqi decoction has shown a protective effect on pancreatic tissue by relieving tissue lesions of pancreas in acute pancreatitis rats. The present study shows this effect correlates to decreased calcium concentration ([Ca2+]i) of pancreatic acinar cells, which is mediated by upregulated sarco/endoplasmic reticulum Ca2+-ATPase mRNA expression of pancreatic tissue.
Acute pancreatitis contributes to more than 200,000 annual hospital admissions in the USA, and such increasing morbidity is also seen in European countries and China. Most patients have a mild and self-limiting condition, needing only brief hospitalization. However, 20% of patients develop severe acute pancreatitis characterized by local and extra-pancreatic complications. Because there is no specific therapeutic option available, the mortality of SAP ranges from 10%-30%.
The major obstacle to the development of therapies is our limited understanding of the pathogenesis of the disease. Among a number of theories that explain the pathogenesis from various aspects, intracellular calcium overload has been generally accepted to play a crucial role in the occurrence and deterioration of acute pancreatitis. Studies on the mechanism of calcium overload have been propelled to a genetic aspect, in which Ca2+-ATPase mRNA expression is involved. Further elucidation of the details will reveal the therapeutic strategies of this disease.
The researchers innovatively selected the valuable and clinically effective herbal compounds Chaiqinchengqi decoction as the subject, according to practical guidelines for management of acute pancreatitis with integrated Chinese traditional and Western medicine. For the first time, the study reveals Chaiqinchengqi decoction has a protective effect on pancreatic tissue by increasing SERCA mRNA expression to relieve intracellular calcium overload. This is a breakthrough and highlight in elucidating the treatment mechanism of Chaiqinchengqi decoction from a genetic aspect.
In the view of the authors, to date no mechanism has been proposed to elucidate the protective effect of Chaiqinchengqi decoction in acute pancreatitis and no literature describes the mechanism of the correlation between Chaiqinchengqi decoction and intracellular calcium overload. Thus, the study aims to investigate the effect of Chaiqinchengqi decoction on SERCA mRNA expression of pancreatic tissue in AP rats.
Because the results intensively ratified the protective effect on pancreatic tissues in an animal experiment on the basis of previous clinical trails and explored genetic treatment mechanism of Chaiqinchengqi decoction in inhibiting intracellular calcium overload, they will enlighten further studies on calcium overload in the treatment of acute pancreatitis
This is pivotal research in exploring the pathogenesis of acute pancreatitis and the treatment mechanism of Chinese herbal compounds, using an excellent study design, including random grouping of rats, an acute pancreatitis model induced by intraperitoneal injection of caerulein, oral administration with Chaiqinchengqi decoction in vivo, pathological observation and scoring of pancreatic tissues by the agreement of pathologists, detection of SERCA1 and SERCA2 mRNA expression in pancreatic tissue with RT-PCR, [Ca2+]i measurement with Fluo-3-AM and laser scanning with a cofocal microscope. Further research is expected to explain the upregulated effect of Chaiqinchengqi decoction on SERCA2 mRNA expression.
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