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Journal of ZheJiang University(Medical Science)  2015, Vol. 44 Issue (3): 278-284    DOI: 10.3785/j.issn.1008-9292.2015.05.07
Sodium cromoglycate attenuates experimental endometriosis in rats by regulating mast cells
ZHU Li-bo, LIN Kai-qing, ZHANG Xin-mei, LIN Jun
Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
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Objective: To investigate the effect of sodium cromoglycate on experimental endometriosis in rats. Methods: Endometriosis model was established in 36 unpregnant female SD rats by transplanting autologous fragments of endometrium to the inner surface of the abdominal wall. The endometriotic lesions were measured by a second laparotomy 2 weeks after surgery. Then the rats were randomly divided into four groups(n=8 in each group) to receive intraperitoneal injection of different doses of sodium cromoglycate for 2 weeks: high-dose group(20 mg·kg-1·d-1); low-dose group(10 mg·kg-1·d-1); the negative control group and the blank control group. The animals were sacrificed and the size of the lesions were measured. The endometriosis model of SD rats was identified by HE staining and immunohistochemical staining of keratin and vimentin. The total number of mast cells and their degranulation were measured by Toluidine blue staining; the concentrations of TNF-α in serum were measured by enzyme linked immunosorbent assay; the concentrations of estradiol in serum were measured by enzyme immunoassay; the expression of tryptase and nerve growth factor(NGF) were measured by immunohistochemical staining. Results: The number of activated mast cells(MC) by Toluidine blue staining in high-dose group was significantly lower than that in negative control group(P<0.05), and its ratio of degranulation/total number of MC was significantly lower than that in negative control group or blank control group(P<0.05). The serum TNF-α levels and tryptase expression in tissues in high-dose group were significantly lower than those in negative control group or blank control group(P<0.05). However, no significant difference in the size of endometriotic lesions and expression of NGF was found among groups(P>0.05). Conclusion: Sodium cromoglycate can stabilize mast cells from degranulation, which may relieve the clinical symptoms of endometriosis by reducing TNF-α and tryptase levels.

Key wordsEndometriosis/pathology      Mast cells/ drug effects      Cromolyn sodium/pharmacology      Cromolyn sodium/administration &      dosage      Cell degranulation      Tumor necrosis factor-alpha      Tryptases      Disease models, animal     
Received: 23 December 2014      Published: 25 May 2015
CLC:  R711.71  
Cite this article:

ZHU Li-bo, LIN Kai-qing, ZHANG Xin-mei, LIN Jun. Sodium cromoglycate attenuates experimental endometriosis in rats by regulating mast cells. Journal of ZheJiang University(Medical Science), 2015, 44(3): 278-284.

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目的:探讨色甘酸钠干预对子宫内膜异位症大鼠肥大细胞的影响及相关机制。方法:取健康雌性未孕SD大鼠36只,采用自体子宫内膜移植法建立大鼠腹壁子宫内膜异位症模型,2周后根据每天腹腔注射不同剂量色甘酸钠将大鼠分为4组:大剂量组(色甘酸钠20 mg/kg)、小剂量组(色甘酸钠10 mg/kg)、阴性对照组(仅注射生理盐水)、空白对照组(模型不作任何处理)。两周后处死大鼠,并收集血液和病灶组织标本,测量各组子宫内膜异位症病灶的大小,并对病灶组织进行苏木素—伊红(HE)染色观察组织形态及角蛋白和波形蛋白免疫组织化学染色以鉴定造模是否成功。用甲苯胺蓝染色法检测各组病灶肥大细胞总数及其脱颗粒肥大细胞数、酶联免疫吸附试验测定血清肿瘤坏死因子α(TNF-α)水平、酶免疫分析法测定血清雌二醇水平、免疫组织化学染色法检测子宫内膜异位症病灶肥大细胞中类胰蛋白酶、神经生长因子的表达水平。结果:大剂量组活化的肥大细胞数少于阴性对照组(P<0.05),脱颗粒肥大细胞数/肥大细胞总数比值大剂量组小于阴性对照组和空白对照组(均P<0.05)。同时,该组血清TNF-α水平、病灶类胰蛋白酶表达均小于阴性对照组和空白对照组(均P<0.05);但经色甘酸钠治疗后子宫内膜异位症病灶神经生长因子表达差异并无统计学意义(均P>0.05)。结论:色甘酸钠可能通过稳定肥大细胞抑制其脱颗粒,减少TNF-α、类胰蛋白酶的释放,改善子宫内膜异位症。

关键词: 子宫内膜异位症/病理学,  肥大细胞/药物作用,  色甘酸钠/药理学,  色甘酸钠/投药和剂量,  细胞脱颗粒,  肿瘤坏死因子&alpha,  类胰蛋白酶类,  疾病模型,  动物 

[1] WANG G, TOKUSHIGE N, MARKHAM R, et al. Rich innervation of deep infiltrating endometriosis [J]. Hum Reprod, 2009, 24(4):827-834.
[2] ZAITSU M, NARITA S, LAMBERT K C, et al. Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx [J]. Mol Immunol, 2007, 44(8):1977-1985.
[3] VERNON M W, WILSON E A. Studies on the surgical induction of endometriosis in the rat [J]. Fertil Steril, 1985, 44(5):684-694.
[4] GIUDICE L C. Clinical practice. Endometriosis [J]. N Engl J Med, 2010, 362(25):2389-2398.
[5] Practice Committee of American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis [J]. Fertil Steril, 2008, 90(5 Suppl):S260-S269.
[6] JACOBSON T Z, DUFFY J M, BARLOW D, et al. Laparoscopic surgery for pelvic pain associated with endometriosis [J]. Cochrane Database Syst Rev, 2014,8:CD001300.
[7] ZHANG G, DMITRIEVA N, LIU Y, et al. Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat [J]. Am J Physiol Regul Integr Comp Physiol, 2008, 294(1):R162-R171.
[8] ASANTE A, TAYLOR R N. Endometriosis: the role of neuroangiogenesis [J]. Annu Rev Physiol, 2011, 73:163-182.
[9] KIRCHHOFF D, KAULFUSS S, FUHRMANN U, et al. Mast cells in endometriosis: guilty or innocent bystanders? [J]. Expert Opin Ther Targets,2012,16(3):237-241.
[10] MATSUZAKI S, CANIS M, DARCHA C, et al. Increased mast cell density in peritoneal endometriosis compared with eutopic endometrium with endometriosis [J]. Am J Reprod Immunol, 1998, 40(4):291-294.
[11] PAULA R J R, OLIANI A H, VAZ-OLIANI D C, et al.The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis [J]. J Mol Histol, 2015,46(1):33-43.
[12] ENGEMISE S L, WILLETS J M, EMEMBOLU J O, et al.The effect of the levonorgestrel-releasing intrauterine system, Mirena® on mast cell numbers in women with endometriosis undergoing symptomatic treatment [J]. Eur J Obstet Gynecol Reprod Biol,2011,159(2):439-442.
[13] 卢韵碧,江 波,周汉良. 沙丁胺醇与色甘酸钠对大鼠腹腔肥大细胞脱颗粒过程中磷脂酶D活性的影响[J].中国药理学与毒理学杂志, 2001, 15(5):366-371 LU Yun-bi, JIANG Bo, ZHOU Han-liang. The effect of salbutamol and sodium cromoglycate on the activity of phospholipase D in the process of intraperitoneal degranulation of mast cells in rats [J]. Chinese Journal of Phamacology and Toxicology, 2001, 15(5):366-371. (in Chinese)
[14] THEOHARIDES T C, WANG L, PANG X, et al. Cloning and cellular localization of the rat mast cell 78-kDa protein phosphorylated in response to the mast cell “stabilizer” cromolyn [J]. J Pharmacol Exp Ther, 2000, 294(3):810-821.
[15] YANG Y, LU J Y, WU X,et al. G-protein-coupled receptor 35 is a target of the asthma drugs cromolyn disodium and nedocromil sodium [J]. Pharmacology, 2010,86(1):1-5.
[16] YAZID S, SINNIAH A, SOLITO E, et al.Anti-allergic cromones inhibit histamine and eicosanoid release from activated human and murine mast cells by releasing Annexin A1 [J]. PLoS One, 2013,8(3):e58963
[17] SHAPIRO G G, KONIG P. Cromolyn sodium: a review [J]. Pharmacotherapy, 1985, 5(3):156-170.
[18] PATALANO F, RUGGIERI F. Sodium cromoglycate: a review [J]. Eur Respir J Suppl, 1989, 6:556s-560s.
[19] VINCENT L, VANG D, NGUYEN J,et al. Mast cell activation contributes to sickle cell pathobiology and pain in mice [J]. Blood, 2013,122(11):1853-1862.
[20] ZUO Y, PERKINS N M, TRACEY D J, et al. Inflammation and hyperalgesia induced by nerve injury in the rat: a key role of mast cells [J]. Pain, 2003, 105(3):467-479.
[21] DIXON M, JACKSON D M, RICHARDS I M. The action of sodium cromoglycate on 'C' fibre endings in the dog lung [J]. Br J Pharmacol, 1980, 70(1):11-13.
[22] KAY A B, WALSH G M, MOGBEL R, et al. Disodium cromoglycate inhibits activation of human inflammatory cells in vitro [J]. J Allergy Clin Immunol, 1987, 80(1):1-8.

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