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[目的]观察急性胰腺炎大鼠LTB4、TRPV1、CGRP等相关指标变化,探讨大黄防治急性胰腺炎的可能机理。[方法]清洁级SD大鼠80只,按体重随机分为4组,正常组、模型组、TRPV1拮抗剂组、大黄治疗组。采用胆胰管开口十二指肠结扎法制备重症胰腺炎模型,术后3h开始分组给药,术后12h处死全部大鼠,腹主动脉取血并收集胰腺组织备测。应用光镜检测胰腺组织超微结构变化,应用ELISA技术检测LTB4变化,应用Real-time PCR技术检测TRPV1、CGRP变化。[结果]正常组胰腺肉眼见胰腺呈浅粉红色;模型组大鼠肉眼见胰腺实质大片坏死、出血和脂肪变性,部分可见含血腹水,光镜下见胰腺腺体结构紊乱,小叶间隔明显增大,腺泡可见大片凝固性坏死并伴有出血,坏死灶及周围有大量炎细胞浸润;TRPV1拮抗剂组大鼠胰腺组织出血及水肿较模型组减轻,少量腹水,浑浊程度低,光镜下胰腺实质可见少许坏死、出血及少量炎性细胞浸润。大黄治疗组未见腹水,病理变化轻,皂化亦明显减轻,胰腺水肿、出血,坏死减轻,其组织病理学评分较模型组下降,有统计学意义(P<0.05)。模型组见血淀粉酶、LTB4表达明显上升,分别为5386.72±190.34、476.52±21.33;TRPV1拮抗剂组血淀粉酶、LTB4表达下降,分别为2315.67±135.42、263.68±15.69,较模型组有统计学意义。大黄治疗组血淀粉酶、LTB4表达明显下降,分别为2136.82±126.72、237.45±12.56,较模型组有统计学意义(P<0.05)。模型组胰腺组织TRPV1、CGRP mRNA表达上升,分别为3.59±1.23、3.08±1.53;TRPV1拮抗剂组TRPV1、CGRP mRNA表达下降,分别为1.82±0.34、1.57±0.26;与模型组比较有统计学意义(P<0.05)。大黄治疗组TRPV1、CGRP mRNA表达明显下降,分别为1.51±0.23、1.28±0.15,较模型组有统计学意义(P<0.05)。[结论]大黄可能通过调节LTB4、TRPV1等炎症因子的表达能发挥防治急性胰腺炎的效用。
[Objective] To observe the changes of LTB4, TRPV1, CGRP and other related indicators in rats with acute pancreatitis and explore the possible mechanism of rhubarb in the prevention and treatment of acute pancreatitis. [Method] Eighty clean grade SD rats were randomly divided into 4 groups according to body weight, normal group, model group, TRPV1 antagonist group and rhubarb treatment group. The model of severe pancreatitis was established by duodenal ligation of biliary and pancreatic ducts. The rats were administered 3h after operation. All rats were sacrificed at 12h after surgery. The abdominal aorta blood was taken and the pancreas tissue was collected and measured. The ultrastructural changes of pancreatic tissue were detected by light microscope. The changes of LTB4 were detected by ELISA. The changes of TRPV1 and CGRP were detected by Real-time PCR. [Result] The pancreas showed light pink in the naked eye of the normal group. In the model group, gross necrosis of the pancreas, hemorrhage and steatosis were observed in the naked eye of the model group. The blood was seen ascites partly. The structure of the pancreas gland was disorganized under light microscope, Large, acinar visible large coagulation necrosis accompanied by hemorrhage, necrosis and a large number of inflammatory cells around the pancreas; TRPV1 antagonist group of pancreatic tissue hemorrhage and edema alleviate the model group, a small amount of ascites, turbidity is low, under light microscopy Pancreatic parenchyma shows a little necrosis, bleeding and a small amount of inflammatory cell infiltration. The rhubarb treatment group showed no ascites, light pathological changes, saponification was also significantly reduced, pancreatic edema, hemorrhage, necrosis reduced, the histopathological score decreased compared with the model group, with statistical significance (P <0.05). In the model group, blood amylase and LTB4 expression were significantly increased (5386.72 ± 190.34 and 476.52 ± 21.33, respectively). The levels of serum amylase and LTB4 in the TRPV1 antagonist group were 2315.67 ± 135.42 and 2663.68 ± 15.69, respectively, which were significantly higher than those in the model group significance. The rhubarb treatment group, serum amylase, LTB4 expression was significantly decreased, respectively, 2136.82 ± 126.72,237.45 ± 12.56, compared with the model group was statistically significant (P <0.05). The expression of TRPV1 and CGRP mRNA in pancreatic tissue of model group increased by 3.59 ± 1.23 and 3.08 ± 1.53, respectively. The mRNA expression of TRPV1 and CGRP in TRPV1 antagonist group decreased by 1.82 ± 0.34 and 1.57 ± 0.26, respectively. Compared with model group, (P <0.05). The expressions of TRPV1 and CGRP mRNA in rhubarb treatment group were significantly decreased, which were 1.51 ± 0.23 and 1.28 ± 0.15, respectively, which were significantly higher than those in model group (P <0.05). [Conclusion] Rhubarb may exert the effect of prevention and treatment of acute pancreatitis by regulating the expression of inflammatory factors such as LTB4 and TRPV1.