The Protective Effects Of Rutaecarpine On Acute Pancreatitis And Its Mechanism

Objective:To investigate the protective effects of rutaecarpine on rats with acute pancreatitis (AP) and through applicating the competitive capsaicin receptor antagonist capsazepine to explore whether the protec-tive effects of rutaecarpine are related to stimulation of endogenous CGRP release via activating vanilloid receptors in rats.Methods:One hundred SD male rats were equally randomized into10groups:(1) sham group,(2) AP group,(3) sham+rutaecarpine group (100μg/kg,iv),(4) AP+rutaecarpine low dose group(30μg/kg,iv),(5) AP+rutaecarpine middle dose group(100μg/kg,iv),(6) AP+rutaecarpine high dose group(30μg/kg,iv),(7) sham+capsazepine group(3mg/kg, iv),(8) AP+capsazepine group (3mg/kg,iv),(9) AP+capsazepine(3mg/kg, iv)+rutaecarpine middle dose group,(10) solvent control group. Except the sham group, the sham+rutaecarpine group and the sham+capsazep-ine group, rats in the rest of other experimental groups were undergone retrograde infution of5%sodium taurocholate into the bilio-pancreatic duct to induce AP model.24hours after modeling, carotid artery was cannulated for collecting blood sample in all rats of each group, and then executed all rats, collected and measured ascitic fluid volume, obtained the pancreatic tissue specimens. Then the pancreatic tissues were stained by hematoxylin-eosin. We evaluated the pancreas gross pathological changes as well as the pancreatic tissue histopathological score. The serum amylase activity was detected by automatic biochemistry analyzer, the serum concentration of IL-6, TNF-a and IL-10were measured by Elisa kits, and radioimmunoassay method for measuring the plasma concentration of CGRP.Results:(1) The pancreatic histopathological examination revealed that:except for the sham group, the sham+rutaecarpine group and the sham+capsazepine group, the rest of other experimental rats developed acute inflammation and necrosis with different degrees, of which, the AP+capsazepine group and the AP+capsazepine+rutaecarpine group both presented the most serious lesions, following by the AP group and solvent control group, the pancreatic inflammation and necrosis was significantly improved in the groups of different dose of rutaecarpine administration, of which the rutaecarpine middle dose group and high dose group showed the slightest lesion. The pancreatic histopathological scoring result showed that the scores of different dose of rutaecarpine groups were significantly lower compared with the AP group (all P<0.05), and paired-comparisons between the three groups also had statistical significance (all P<0.05). The scores of AP group and solvent control group were close, they had no statistical significance (P>0.05). However the AP+capsazepine group and the AP+capsazepine+rutaecar-pine group both acquired higher scores than the AP group (all P<0.05), and the AP+capsazepine+rutaecarpine group also significantly scoring more than rutaecarpine middle dose groups (P<0.05).(2) The ascitic fluid volume of AP group and solvent control group were significantly high than that of the sham group, while the sham group, the sham+rutaecarpine group and the sham+capsazepine group both were observed only few ascitic fluid. Administration of different dose of rutaecarpine before modeling could significantly reduce ascitic fluid volume of rats, while administration capsazepine ahead of rutaecarpine could increased ascitic fluid volume of rats.(3) The serum amylase activity was maintained at low level both in the sham group, the sham+rutaecarpine group and the sham+capsazepine group, but significantly increased in the AP group and the solvent control group (P<0.05). Administration of rutaecarpine could markedly decreased serum amylase activity compared with the AP group (both P<0.05), especially in the middle and high dose group. On the contrary, serum amylase activity significantly increased more than that of AP group after administration of capsazepine ahead of rutaecarpine before modeling (both P<0.05).Moreover, the serum amylase activity of the AP+capsaz-epine+rutaecarpine middle dose group was more higher than that of rutaecarpine middle dose group.(4) The serum concentration of IL-6and TNF-α both stayed low levels in rats of the sham group, the sham+rutaecarpine group and the sham+capsazepine group, while increased in the rest of experimental group rats with different degrees (both P<0.05). Different dose of rutaecarpine administration before modeling significa-ntly reduced serum concentration of IL-6and TNF-α, especially in the rutaecarpine middle and high group rats(both P<0.05). However serum concentration of IL-6and TNF-α were further increased after administration capsazepine before modeling (both P<0.05). The serum concentration of IL-10groups were increased with different degrees after administration rutecarpine (both P<0.05), and both in the AP group and solvent control group, it also increased slightly (P<0.05); but it decreased in rats of the groups which were administration capsazepine before experiment (both P<0.05).(5) The plasma concentration level of CGRP of the AP group was slightly increased compared with the sham group (P<0.05), as well as the solvent control group (P<0.05). The plasma concentration level of CGRP was significantly increased with different degrees in different dose of rutecarpine group, of which the rutaecarpine high dose group was the highest (all P<0.05). But the plasma concentration level of CGRP was markedly decreased after administration capsazepine before modeling, similar to the sham group (P>0.05). The plasma CGRP concentration level of both the AP+capsa-zepine group and the AP+capsazepine+rutaecarpine group was lower compared with the rutaecarpine middle dose group (P<0.05).Conclusion:1. Rutaecarpine possesses protective effects on AP.2. The protective effects of rutaecarpine are related to stimulation of endogenous CGRP release via activating vanilloid receptors in rats. Rutaecarpine improves the microcirculation of the pancreatic tissue, reduces the proinflammatory cytokines liberation and increases the anti-inflammatory cytokines liberation, and then improves the degree of pancreatic tissue inflammation and necrosis. Its protective effects could be blocked by capsazepine.