期刊论文详细信息
BMC Complementary and Alternative Medicine
Protective effect of Xuebijing injection on paraquat-induced pulmonary injury via down-regulating the expression of p38 MAPK in rats
Chuan-yun Qian3  Li Wang3  Mei Chen2  Yan-qiong Wang1  Wei Zhang3  Mei-xian Su4  Ming-wei Liu3 
[1]Department of Anesthesiology, The First Hospital Affiliated To Kunming Medical University, 295 Xichang Road, Wu Hua District, Kunming 650032, China
[2]Department of Respiratory Medicine, The Yan-an Hospital Affiliated To Kunming Medical University, 245 Renmin Eastern Road, Pan Long District, Kunming 650051, China
[3]Department of Emergency, The First Hospital Affiliated To Kunming Medical University, 295 Xichang Road, Wu Hua District, Kunming 650032, China
[4]Intensive Care Unit, The Second Hospital Affiliated To Kunming Medical University, 1 Mayuan, Wu Hua District, Kunming 650106, China
关键词: Rat;    NF-κB65;    p38 MAPK;    Acute lung injury;    Paraquat;    Xuebijing;   
Others  :  1084699
DOI  :  10.1186/1472-6882-14-498
 received in 2013-12-07, accepted in 2014-12-10,  发布年份 2014
PDF
【 摘 要 】

Background

Exposure to paraquat results in acute lung injury. A systemic inflammatory response has been widely established as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of Xuebijing prevents inflammatory response-induced diseases. This study investigated whether consumption of Xuebijing protected rats against paraquat-induced acute lung injury.

Methods

Adult male Sprague Dawley rats were randomly divided into four groups: control group; paraquat group; paraquat + Xuebijing group; and paraquat + dexamethasone group. Rats in the paraquat, paraquat + Xuebijing and paraquat + dexamethasone groups were intraperitoneally injected with paraquat (30 mg/kg) or administered paraquat and Xuebijing at 8 mL/kg or dexamethasone at 5 mg/kg, respectively, via an injection into the tail vein. Lung p38 MAPK, NF-κB65, IkB, p-IκB-α, HIF-1α, Nrf2 and TGF-β1 expression were essayed using western blotting. IL-6, TNF-α, IL-1β, IL-10, TGF-β1 and PIIIP were measured using ELISA. ROS, oxidised glutathione and glutathione activity were measured.

Results

After inducing acute lung injury with paraquat for 24 h, Xuebijing was observed to block lung p-p38 MAPK, NF-κB65, HIF-1α, p-IκB-α and TGF-β1 expression, and increased Nrf2 and IkB expression. The numbers of neutrophils and lymphocytes and total number of cells were significantly lower in the Xuebijing group compared with the control group. IL-6, TNF-α, IL-1β, TGF-β1 and PIIIP levels were significantly decreased in the Xuebijing group. ROS and oxidised glutathione activity were markedly inhibited by Xuebijing. Histological evaluation showed attenuation of the effects of Xuebijing on paraquat-induced lung injury. Compared with the paraquat + dexamethasone group, the Xuebijing + paraquat group showed no significant differences.

Conclusions

Inhibiting the expression of p38 MAPK and NF-κB65 was crucial for the protective effects of Xuebijing on paraquat-induced acute lung injury. The findings suggest that Xuebijing could effectively ameliorate paraquat-induced acute lung injury in rats. Xuebijing was as effective as dexamethasone at improving paraquat-induced lung injury by regulating lung inflammation, lung function and oxidative stress responses.

【 授权许可】

   
2014 Liu et al.; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150113163639933.pdf 2128KB PDF download
Figure 10. 70KB Image download
Figure 9. 38KB Image download
Figure 8. 37KB Image download
Figure 7. 48KB Image download
Figure 6. 53KB Image download
Figure 5. 40KB Image download
Figure 4. 119KB Image download
Figure 3. 76KB Image download
Figure 2. 129KB Image download
Figure 1. 65KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

【 参考文献 】
  • [1]DU Y, Mou Y: Predictive value of 3 methods in severity evaluation and prognosis of acute paraquat poisoning. Zhong Nan Da Xue Bao Yi Xue Ban 2013, 8:737-742. Chinese
  • [2]Choi JS, Jou SS, Oh MH, Kim YH, Park MJ, Gil HW, Song HY, Hong SY: The dose of cyclophosphamide for treating paraquat-induced rat lung injury. Korean J Intern Med 2013, 28:420-427.
  • [3]Yin Y, Guo X, Zhang SL, Sun CY: Analysis of Paraquat Intoxication Epidemic (2002–2011) within China. Biomed Environ Sci 2013, 26:509-512.
  • [4]Amirshahrokhi K: Anti-inflammatory effect of thalidomide in paraquat-induced pulmonary injury in mice. Int Immunopharmacol 2013, 17:210-215.
  • [5]Tian ZG, Ji Y, Yan WJ, Xu CY, Kong QY, Han F, Zhao Y, Pang QF: Methylene blue protects against paraquat-induced acute lung injury in rats. Int Immunopharmacol 2013, 17:309-313.
  • [6]Chen J, Zeng T, Bi Y, Zhong Z, Xie K, Zhao X: Docosahexaenoic acid (DHA) attenuated paraquat induced lung damage in mice. Inhal Toxicol 2013, 25:9-16.
  • [7]Tomita M, Okuyama T, Katsuyama H, Miura Y, Nishimura Y, Hidaka K, Otsuki T, Ishikawa T: Mouse model of paraquat-poisoned lungs and its gene expression profile. Toxicology 2007, 231:200-209.
  • [8]Lin JL, Lin-Tan DT, Chen KH, Huang WH: Repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe paraquat poisoning. Crit Care Med 2006, 34:368-373.
  • [9]Zhang LY, Li M, Tao CJ, Ye JM: The Situation of paraquat poisoning and management suggestions. Pesticide Sciand Admin 2011, 32:10-13.
  • [10]Liu Y, Liu Z: Analysis of prognostic factor after paraqua poisoning. Chin J Crit Care Med 2005, 25:679-681.
  • [11]Eddleston M, Wilks MF, Buckley NA: Prospects for treatment of paraquat-induced lung fibrosis with immunosuppressive drugs and the need for better prediction of outcome: a systematic review. QJM 2003, 96:809-824.
  • [12]Licker M, Schweizer A, Hohn L, Morel DR, Spiliopoulos A: Single lung transplantation for adult respiratory distresssyndrome after paraquat poisoning. Thorax 1998, 53:620-621.
  • [13]Laurent GJ, Coker RK, McAnulty RJ: TGF-beta antibodies: a novel treatment for pulmonary fibrosis? Thorax 1993, 48:953-954.
  • [14]He Q, Chen HX, Li W, Wu Y, Chen SJ, Yue Q, Xiao M, Li JW: IL-36 cytokine expression and its relationship with p38 MAPK and NF-κB pathways in psoriasis vulgaris skin lesions. J Hua Zhong Univ Sci Technolog Med Sci 2013, 33:594-599.
  • [15]Wang HW, Wu T, Qi JY, Wang YQ, Luo XP, Ning Q: Salidroside attenuates LPS-stimulated activation of THP-1 cell-derived macrophages through down-regulation of MAPK/NF-kB signaling pathways. J Huazhong Univ Sci Technolog Med Sci 2013, 33:463-469.
  • [16]Chen Y, Tong H, Zhang X, Tang L, Pan Z, Liu Z, Duan P, Su L: Xuebijing injection alleviates liver injury by inhibiting secretory function of Kupffer cells in heat stroke rats. J Tradit Chin Med 2013, 33:243-249.
  • [17]Fang K, Wang XL: Treatment of multiple organ dysfunction syndrome by Xuebijing Injection: a clinical research. Zhongguo Zhong Xi Yi Jie He Za Zhi 2013, 33:205-207.
  • [18]Jiang M, Zhou M, Han Y, Xing L, Zhao H, Dong L, Bai G, Luo G: Identication of NF-κB Inhibitors in Xuebijing injection for sepsis fitreatment based on bioactivity-integrated UPLC-Q/TOF. J Ethnopharmacol 2013, 147:426-433.
  • [19]Noble WH, Obdrzalek J, Kay JC: A new technique for measuring pulmonary edema. J Appl Physiol 1973, 34:508-512.
  • [20]Sakuma T, Hida M, Nambu Y, Osanai K, Toga H, Takahashi K, Ohya N, Inoue M, Watanabe Y: Effects of hypoxia on alveolar fluid transport capacity in rat lungs. J Appl Physiol 2001, 91:1766-1774.
  • [21]Biswas S, Gupta MK, Chattopadhyay D, Mukhopadhyay CK: Insulin induced activation of hypoxia-inducible factor-1 requires generation of reactiveoxygen species by NADPH oxidase. Am J Physiol Heart Circ Physiol 2007, 292:H758-H766.
  • [22]Wang X, Nelin LD, Kuhlman JR, Meng X, Welty SE, Liu Y: The role of MAP kinase phosphatase-1 inthe protective mechanism of dexamethasone against endotoxemia. Life Sci 2008, 83:671-680.
  • [23]Annane D: Glucocorticoids in the treatment of severe sepsis and septic shock. Curr Opin Crit Care 2005, 11:449-453.
  • [24]Wong HR, Cvijanovich NZ, Allen GL, Thomas NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Weiss SL, Shanley TP, Bigham MT, Banschbach S, Beckman E, Harmon K, Zimmerman JJ: Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock. Am J Respir Crit Care Med 2014, 189:940-946.
  • [25]Phan SH, Thrall RS, Williams C: Bleomycin-induced pulmonary fibrosis.Effects of steroid on lung collagen metabolism. Am Rev Respir Dis 1981, 124:428-434.
  • [26]Koenig WJ, Cross CE, Hesterberg TW, Last JA: The smoking gun. Mechanism of methylprednisolone prevention of bleomycin-induced pulmonary fibrosis. Chest 1983, 83:5S-7S.
  • [27]Grunze MF, Parkinson D, Sulavik SB, Thrall RS: Effect of corticosteroids on lung volume-pressure curves in bleomycin- induced lung injury in the rat. Exp Lung Res 1988, 14:183-195.
  • [28]Sun ML, Ma DH, Liu M, Yu YX, Cao DB, Ma C, Wang X, Liu XL: Successful treatment of paraquat poisoning by Xuebijing, an injection concocted from multiple Chinese medicinal herbs: a case report. J Altern Complement Med 2009, 15:1375-1378.
  • [29]Rocco PRM, Negri EM, Kurtz PM: Vasconcellos FP, Silva GH, Capelozzi VL, Romero PV, Zin WA: Lung tissue mechanics and extracellular matrix remodeling in acute lung injury. Am J Respir Crit Care Med 2001, 164:1067-1071.
  • [30]Rocco PR, Souza AB, Faffe DS, Pássaro CP, Santos FB, Negri EM, Lima JG, Contador RS, Capelozzi VL, Zin WA: Effect of corticosteroid on lung parenchyma remodeling at an early phase of acute lung injury. Am J Respir Crit Care Med 2003, 168:677-684.
  • [31]Sittipunt C: Paraquat poisoning. Respir Care 2005, 50:383-385.
  • [32]Sun YN, Li W, Yan XT, Yang SY, Song SB, Kim YH: Phenolic components from the stem of Acanthopanax koreanum and their inhibitory effects on NF-kappa B. Biosci Biotechnol Biochem 2014, 78:374-377.
  • [33]Jacobs MD, Harrison SC: Structure of an IkappaBalpha/NF-kappaB complex. Cell 1998, 95:749-758.
  • [34]Verma IM, Stevenson JK, Schwarz EM, Van Antwerp D, Miyamoto S: Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev 1995, 9:2723-2735.
  • [35]Nadeem A, Siddiqui N, Alharbi NO, Alharbi MM, Imam F: Acute glutathione depletion leads to enhancement of airway reactivity and inflammation via p38MAPK-iNOS pathway in allergic mice. Int Immunopharmacol 2014, 22:222-229.
  • [36]Holen E, Espe M, Andersen SM, Taylor R, Aksnes A, Mengesha Z, Araujo P: A co culture approach show that polyamine turnover is affected during inflammation in Atlantic salmon immune and liver cells and that arginine and LPS exerts opposite effects on p38MAPK signaling. Fish Shellfish Immunol 2014, 37:286-298.
  • [37]Guo R, Wu K, Chen J, Mo L, Hua X, Zheng D, Chen P, Chen G, Xu W, Feng J: Exogenous hydrogen sulfide protects against doxorubicin-induced inflammation and cytotoxicity by inhibiting p38MAPK/NFκB pathway in H9c2 cardiac cells. Cell Physiol Biochem 2013, 32:1668-1680.
  • [38]Lan A, Xu W, Zhang H, Hua X, Zheng D, Guo R, Shen N, Hu F, Feng J, Liu D: Inhibition of ROS-activated p38MAPK pathway is involved in the protective effect of H2S against chemical hypoxia-induced inflammation in PC12 cells. Neurochem Res 2013, 38:1454-1466.
  • [39]Tasaka S, Amaya F, Hashimoto S, Ishizaka A: Roles of oxidants and redox signaling in the pathogenesis of acute respiratory distress syndrome. Antioxid Redox Signal 2008, 10:739-753.
  • [40]Roper JM, Mazzatti DJ, Watkins RH, Maniscalco WM, Keng PC, O’Reilly MA: In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells. Am J Physiol Lung Cell Mol Physiol 2004, 286:L1045-L1054.
  • [41]Barazzone C, Horowitz S, Donati YR, Rodriguez I, Piguet PF: Oxygen toxicity in mouse lung: pathways to cell death. Am J Respir Cell Mol Biol 1998, 19:573-581.
  • [42]Lee YC, Lee KS, Park SJ, Park HS, Lim JS, Park KH, Im MJ, Choi IW, Lee HK, Kim UH: Blockade of airway hyperresponsiveness and inflammation in a murine model of asthma by a prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid. FASEB J 2004, 18:1917-1919.
  • [43]Tanabe T, Fujimoto K, Yasuo M, Tsushima K, Yoshida K, Ise H, Yamaya M: Modulation of mucus production by interleukin-13 receptor alpha2 in the human airway epithelium. Clin Exp Allergy 2008, 38:122-134.
  • [44]Yasuo M, Fujimoto K, Tanabe T, Yaegashi H, Tsushima K, Takasuna K, Koike T, Yamaya M, Nikaido T: Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells. Respiration 2006, 73:347-359.
  • [45]Cheng SE, Lee IT, Lin CC, Kou YR, Yang CM: Cigarette smoke particle-phase extract induces HO-1 expression in human tracheal smooth muscle cells: Role of the c-Src/NADPH oxidase/MAPK/Nrf2 signaling pathway. Free Radic Biol Med 2010, 48:1410-1422.
  • [46]Papaiahgari S, Zhang Q, Kleeberger SR, Cho HY, Reddy SP: Hyperoxia stimulates an Nrf2-ARE transcriptional response via ROS-EGFR-PI3K-Akt/ERK MAP kinase signaling in pulmonary epithelial cells. Antioxid Redox Signal 2006, 8:43-52.
  • [47]Koshikawa N, Hayashi J, Nakagawara A, Takenaga K: Reactive oxygen species-generating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-1alpha gene transcription via phosphatidylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway. J Biol Chem 2009, 284:33185-33194.
  • [48]Kotecha S, Wangoo A, Silverman M, Shaw RJ: Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity. J Pediatr 1996, 128:464-469.
  • [49]Painemal P, Acuña MJ, Riquelme C, Brandan E, Cabello-Verrugio C: Transforming growth factor type beta 1 increases the expression of angiotensin II receptor type 2 by a SMAD- and p38 MAPK-dependent mechanism in skeletal muscle. Biofactors 2013, 39:467-475.
  • [50]Kjeldsen J, de Schaffalitzky Muckadell OB, Junker P: Seromarkers of collagen I and III metabolism in active Crohn's disease. Relation to disease activity and response to therapy. Gut 1995, 37:805-810.
  • [51]Stallmach A, Schuppan D, Riese HH, Matthes H, Riecken EO: Increased collagen type III synthesis by fibroblasts isolated from strictures of patients with Crohn’s disease. Gastroenterology 1992, 102:1920-1929.
  • [52]Blois A, Srebro B, Mandalà M, Corti A, Helle KB, Serck-Hanssen G: The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells. Regul Pept 2006, 135:78-84.
  • [53]Shah D, Romero F, Stafstrom W, Duong M, Summer R: Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury. Am J Physiol Lung Cell Mol Physiol 2014, 306:L152-L161.
  • [54]Rehberg S, Yamamoto Y, Sousse LE, Jonkam C, Zhu Y, Traber LD, Cox RA, Prough DS, Traber DL, Enkhbaatar P: Antithrombin attenuates vascular leakage via inhibiting neutrophil activation in acute lung injury. Crit Care Med 2013, 41:e439-e446.
  • [55]Li HF, Sun ML, Yu YX, Liu XL: Xuebijing alters tumor necrosis factor-alpha, interleukin-1beta and p38 mitogen activated protein kinase content in a rat model of cardiac arrest following cardiopulmonary resuscitation. Neural Regen Res 2011, 6:2573-2576.
  • [56]Liu QQ, Zhu XQ, Wang L: Effects of Xuebijing injection on survival rats and liver-kidey function in rats with sepsis. JETCM 2008, 17:203-205.
  文献评价指标  
  下载次数:59次 浏览次数:18次