直接肾素抑制剂对大鼠急性胰腺炎的保护作用及机制  

Protective effects of aliskiren, a direct renin inhibitor, in rats with acute pancreatitis

作　　者：黄元龙[1] 尹青[1] 颜琼[1] 邓明明[1] 

机构地区：[1]泸州医学院附属医院消化内科,四川省泸州市646000

出　　处：《世界华人消化杂志》2014年第13期1841-1847,共7页World Chinese Journal of Digestology

基　　金：泸州市科技计划基金资助项目;No.2013-S-48(3/30)~~

摘　　要：目的:探讨直接肾素抑制剂(阿利吉仑)抑制肾素-血管紧张素系统(renin-angiotensin system,RAS)首位环节对大鼠急性胰腺炎(acute pancreatitis,AP)的保护作用及机制.方法:72只SD大鼠随机分为假手术组(SO组)、急性胰腺炎组(AP组)、阿利吉仑治疗组(R组).采用3.5%牛磺胆酸钠(0.1 mL/100 g)逆行胰胆管注射制备AP组和R组大鼠急性胰腺炎模型;而SO组仅开腹并轻轻触动十二指肠和胰腺后关腹.R组于造模成功后给予阿利吉仑溶液灌胃(20 mg/kg);SO组及AP组给予同等剂量的生理盐水灌胃.各组大鼠于术后6、12、24 h,分批次等数量[8只/(组·批)]下腔静脉抽血后处死.取胰腺组织观察胰腺病理变化及进行病理学评分,并检测大鼠血清淀粉酶(serum amylase,AMY)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、血浆肾素活性(plasma enin activity,PRA)的变化.免疫组织化学方法观察胰腺组织血管紧张素Ⅱ1型受体(angiotensinⅡtype 1 receptor,AT1R)血管紧张素Ⅱ1型受体(AT1R)和核因子-kB(nuclear factor kappa-B,NF-kB)的表达情况.结果:与AP组比较,R组各时间点(6、12、24h)的病理学评分(7.25±0.80、9.57±1.54、12.75±1.22)、AMY(2230.87 U/L±224.71 U/L、2137.41 U/L±193.31 U/L、2457.01 U/L±188.81 U/L)、TNF-α(26.28 ng/L±2.45 ng/L、27.51 ng/L±1.91 ng/L、27.17 ng/L±2.02 ng/L),PRA[7.31 ng/(mL·h)±1.94 ng/(mL·h)、8.69ng/(mL·h)±1.78 ng/(mL·h)、9.04 ng/(mL·h)±1.78 ng/(mL·h)]和AngⅡ(755.47 ng/L±121.33ng/L、871.17 ng/L±129.43 ng/L、878.39 ng/L±81.29 ng/L)明显降低(P<0.05),AT1受体阳性表达率(48.60%±6.28%、49.62%±7.19%、51.20%±7.04%)下降(P<0.05),以及NF-kB的阳性表达率(65.66%±4.93%、68.66%±5.23%、68.13%±7.14%)亦下降(P<0.05).结论:肾素抑制剂(阿利吉仑)对大鼠急性胰腺炎的炎症病变及损伤具有一定保护作用.AIM： To investigate the inhibitory effects of aliskiren on the renin angiotensin system （RAS） in rats with acute pancreatitis （AP） and to explore the mechanisms involved. METHODS： Seventy-two SD rats were randomly divided into a sham operation group, an acute AP model group, and an aliskiren therapy group. AP was induced by retrograde injection of 3.5% sodium taurocholate （0.1 mL/100 g） into the biliopancreatic duct. Aliskiren solution was administered in rats of the aliskiren therapy group by garage at a dose of 20 mg/kg, and equivalent volume of normal saline （NS） was given in the other two groups. Rats in each group were further divided into three subgroupsfor taking inferior vena cava blood samples at 6, 12 and 24 h, respectively. The rats were then killed to observe pancreatic pathological changes and measure serum amylase （AMY）, tumor necrosis factor-α （TNF-α）, angiotensin Ⅱ （AngⅡ）, and plasma renin activity （PRA）. The expression of nuclear factor kappa-B （NF-κB） and angiotensin Ⅱ type Ⅰ receptor （ATIR） in the pancreas was determined by immunohistochemistry. RESULTS： Compared with the AP group, pancreatic histopathological score （7.25 ± 0.80, 9.57 ± 1.54, 12.75 ± 1.22）, AMY （2230.87 U/L ± 224.71 U/L, 2137.41 U/L ：t： 193.31 U/L, 2457.01 U/L ± 188.81 U/L）, TNF-α （26.28 ng/L ± 2.45 ng/L, 27.51 ng/L ± 1.91 ng/L, 27.17 ng/L ± 2.02 ng/L）, PRA [7.31 ng/（mL,h） ± 1.94 ng/（mL.h）, 8.69 ng/（mL.h） ± 1.78 ng/（mL·h）, 9.04 ng/（mL·h） ± 1.78 ng/（mL·h）], Ang II （755.47 ng/L ± 121.33 ng/L, 871.17 ng/L ± 129.43 ng/L, 878.39 ng/L ± 81.29 ng/L）, positive rates of ATIR （48.60 ± 6.28, 49.62± 7.19, 51.20 ± 7.04） and NF-κB （65.66 ± 4.93, 68.66 ± 5.23, 68.13 ± 7.14） at each time point （6, 12, 24 h） were decreased significantly （P 〈 0.05 for all） in the aliskiren therapy group. CONCLUSION： Aliskiren can protect from pancreatic inflammation and injury in AP rats.

关 键 词：急性胰腺炎 直接肾素抑制剂 阿利吉仑 肾素-血管紧张素系统 

分 类 号：R657.51[医药卫生—外科学]