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| Effects of Rhubarb on brain dysfunction in septic rats |
| Guo A-ru, Ma Li, Li Du-peng, Zhang Bei, An Hong |
| Department of Emergency Intensive Care Unit, the Second Hospital of Lanzhou University, Lanzhou 730030, China |
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Abstract Objective: To investigate the effect of Rhubarb on brain dysfunction in septic rats. Methods: A total of 84 Wistar male rats were randomly divided into three groups(n=28 each), sham operation group(Sham), cecal ligation and puncture group(CLP), Rhubarb+ CLP group(R+CLP). Every group was then divided into two subgroups(A and B). Female rats were gavaged daily(1 mL/100 g body weight)with Rhubarb for three days. The same dose of saline was used in the control groups. Septic rat model was established by CLP. Survival rate was monitored in A groups, 10 days totally. In B groups, animals were euthanized at 12, 24 and 48 hours after CLP. Wet-dry weighting method was used to detect the brain water content(BWC). The ELISA method was employed to determine the concentrations of plasma S100β, neuron-specific enolase(NSE)and the protein expression levels of brain tissue NF-κB, IL-6 and TNF-α. Then Hematoxylin and Eosin(HE)staining was used to detect brain pathologic change. Immunohistochemical SP method was applied to count the number of AQP-4 positive glial cells in brain tissues. Results: ①The BWC values of the CLP and R+CLP group at all time points were significantly higher than those of the sham group at the same periods(P＜0.05), and which was lower in R+CLP group than that in CLP group at 6h after CLP(P＜0.05). ②CLP and R+CLP groups brain tissue levels of NF-κB, IL-6, and TNF-α were significantly increased compared with Sham group at each moment after CLP(P＜0.05), and R+CLP group brain tissue levels of NF-κB, IL-6, and TNF-α were also significantly lower than the CLP group at 24 h after CLP(P＜0.05). ③Compared with Sham group, the concentrations of plasma S100β, NSE were notably increased after CLP at each moment(P＜0.05), and which were significantly reversed by treatment with Rhubarb at 24 h after CLP(P＜0.05). ④Brain tissue HE staining showed the pathological damage were lightest in the sham group, however, the pathological damage in the CLP group was the most serious degree, and compared with the CLP group, the pathological damage was significantly decreased in the R+CLP group at 6h after CLP(P＜0.05). ⑤The AQP-4 positive gliacyte cells in brain tissues in the CLP group were more than those in the sham group at each time(P＜0.05), but were significantly fewer than those in the CLP group at 6h after CLP(P＜0.05). There was a significantly positive correlation between AQP-4 expression and brain water content(r=0.895, P＜0.05). ⑥Rhubarb could prevented mortality in septic rats. Conclusion: Rhubarb can inhibit the expressions of IL-6, and TNF-α proteins in rats with sepsis by inhibiting NF-κB signaling pathway, and ameliorate the CLP-induced brain tissue edema by down-regulating the expression of the brain gliacyte AQP-4.
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Received: 01 March 2017
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| About author:: Guo A-ru, E-mail: aruguo0126@163.com |
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| ［1］曾朝涛,蒋龙元. 脓毒症相关性脑病研究进展［J］. 岭南急诊医学杂志, 2011, 16(6):494-497.
［2］李建生，刘敬霞，王冬，等. 大黄苷元注射抗大鼠脑缺血损伤炎性级联反应［J］.中国药理学报, 2007, 23(1):114-118.
［3］唐宇平，蔡定芳，刘军，等. 急性脑出血血肿周围组织水通道蛋白-4表达与血脑屏障损伤的关系［J］. 中华神经科杂志, 2005, 38(11):704-708.
［4］Bajic JE, Eden GL, Lampton LS，et al. Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis［J］. World J Gastroenterol, 2016, 22(37): 8322–8333.
［5］Baker CC, Chaudry IH, Gaines HO, et al. Evaluation of factors affecting mortality rate after sepsis in a murine cecal ligation and puncture model［J］.Surgery, 1983, 94(2):331-335.
［6］Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and sepsis shock(sepsis-3)［J］. JAMA, 2016, 315(8):801-810.
［7］Shankar-Hari M, Phillips GS, Levy ML, et al. Sepsis definitions task force:developing a new definition and assessing new clinical criteria for septic shock: the third international consensus definitions for sepsis and sepsis shock(sepsis-3)［J］. JAMA, 2016, 315(8):775-787.
［8］Seymour CW, Liu VX, Iwashyna TJ , et al. Assessment of clinical criteria for sepsis: the third international consensus definitions for sepsis and sepsis shock(sepsis-3)［J］. JAMA, 2016, 315(8):762-774.
［9］Angus DC, Linde-Zwirble WT, Lidicker J , et al. Epidemiology of severe sepsis in the united states: analysis of incidence,outcome,and associated costs of care［J］. Crit Care Med, 2001, 29(7):1302-1310.
［10］Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the united states from 1979 through 2000［J］. N Engl J Med, 2003, 348(16):1546-1554.
［11］Gofton TE, Young GB. Sepsis-associated encephalopathy［J］. Nat Rev Neurol, 2012, 8(10):557-566.
［12］Tian H, Zhang M, Du C,et al. Effects of Rhubarb combined with ulinastatin on T-cell subsets in sepsis rats［ J］. Int J Clin Exp Med, 2015, 8(1):1234-1240.
［13］Pan MH, Lai CS, Ho CT, et al. Anti-inflammatory activity of natural dietary flavonoids［J］. Food Funct, 2010, 1(1):15-31.
［14］Ding RB, Tian K, Huang LL, et al. Herbal medicines for the prevention of alcoholic liver disease: a review［J］. J Ethnopharmacol, 2012, 144(3):457-465.
［15］Huang Q, Lu G, Shen HM, et al. Anti-cancer properties of anthraquinones from rhubarb［J］. Med Res Rev, 2007, 27(5):609-630.
［16］Orman ES, Odena G, Bataller R , et al. Alcoholic liver disease: pathogenesis, management, and novel targets for therapy［J］. J Gastroenterol Hepatol, 2013, 28(1):77-84.
［17］Peigen X, Liyi H, Liwei W. Ethnopharmacologic study of Chinese rhubarb［ J］. J Ethnopharmacol,1984, 10(3): 275-293.
［18］Liu L, Guo Z, Lv Z, et al. The beneficial effects of of Rheum tanguticum polysaccharide onprotecting against diarrhea, colonic inflammation andulceration in rats with TNBS-induced colitis: the role of macrophage mannose receptor in inflammation and immune response［J］. Int Immunopharmacol, 2008, 8(11):1481-1492.
［19］Qin YJ, Wang JB, Kong WJ, et al. The diarrhoeogenic and antidiarrhoeal bidirectional effects of rhubarb and its potential mechanism［J］. J Ethnopharmacol, 2011, 133(3):1096-1102.
［20］Tian H, Zhang M, Du C, et al. Effects of Rhubarb combined with ulinastatin on T-cell subsets in sepsis rats［J］. Int J Clin Exp Med, 2015, 8(1):1234–1240.
［21］Chen DC, Ma LQ, Liu SZ, et al. Effects of Rhubarb on intestinal flora and bacterial translocation in rats with sepsis［J］. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 2009, 21(1):17-20.
［22］Thomason MH, Payseur ES, Hakennewerth AM , et al. Nosocomial pneumonia in ventilated trauma patients during stress ulcer prophylaxis with sucralfate, antacid,and ranitidine［J］. J Trauma, 1996, 41(3):503-508.
［23］Neyrinck AM, Etxeberria U, Taminiau B , et al. Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota［J］. Mol Nutr Food Res, 2017, 61(1)， Epub 2016 Jun 1.
［24］Lai F, Zhang Y, Xie DP, et al. A systematic review of rhubarb(a traditional Chinese medicine)used for the treatment of experimental sepsis［J］. Evid Based Complement Alternat Med, 2015, 2015:131 283
［25］张衍，王焕成，宋明爱. 依达拉奉改善大鼠血脑屏障损伤的AQP-4 机制研究［J］. 中国实用神经疾病杂志, 2010, 13(2):5-7.
［26］Eefsen M, Jelnes P, Schmidt LE, et al. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema［J］. Metab Brain Dis, 2010, 25(3):315-323.
［27］任丽，孙善全. 脑缺血再灌注后AQP4mRNA表达及其与BBB通透性改变的关系［J］. 中华神经科杂志, 2004, 37(4):303.
［28］Vizuete ML, Venero JL, Vargas C, et al. Differential up-regulation of aquaporin-4 mRNA expression in reactive astrocytes after brain injury: potential role in edema［J］. Neurobiol Dis, 1999, 6(4):245-258.
［29］Saadoun S, Papadopoulos MC, Davies DC, et al. Aquaporin-4 expression is increased in oedematous human brain tumors［J］. J Neurol Neurosurg Psychiary, 2002, 72(2):262-265.
［30］Lee AS, Jung YJ, Thanh TN, et al. Paricalcitol attenuates lipopolysaccharide-induced myocardial inflammation by regulating the NF-κB signaling pathway［J］. Int J Mol Med, 2016, 37(4):1023-1029.
［31］Chaudhry N, Duggal AK. Sepsis associated encephalopathy［J］. Nat Rev Neurol, 2012, 8(10):557-566.
［32］Terrando N, Rei Fidalgo A, Vizcaychipi M, et al.The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction［J］. Crit Care, 2010, 14(3):R88.
［33］王雪飞，李彬，刘清泉，等. 脓毒症相关性脑病的发病机制及治疗探讨［J］. 世界中医药, 2014, 9(3):281-284.
［34］Rothermundt M, Peters M, Prehn JH, et al. S100B in brain damage and neurodegeneration［ J］. Microsc Res Tech, 2003, 60(6):614-632.
［35］Kanner AA, Marchi N, Fazio V, et al. Serum S100beta:A noninvasive marker of blood-brain barrier function and brain lesions［J］. Cancer, 2003, 97(11):2806-2813.
［36］Woertgen C, Rothoerl RD, Brawanski A. Neuron - specific enolase serum levels after controlled cortical impact injury in the rat［J］. J Neurotrauma, 2001, 18(5):569-573. |
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