EP2受体在猕猴肾组织中的表达分布研究
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摘要
目的研究前列腺素E2受体EP2在正常猕猴肾组织的表达和分布情况,讨论EP2的分布特点与肾功能之间的相关性。方法将制备好的猕猴肾脏石蜡切片进行HE染色,在光镜下进行肾脏组织结构的辨别。采用免疫组织化学SP法观察EP2在肾脏中的免疫阳性表达,用HP IAS1000高清图像分析系统对HE染色和免疫组化实验结果进行观察和图像采集。结果 EP2的免疫阳性表达产物为棕色,它在肾脏各个区域的表达分布情况不同。免疫组织化学结果表明,EP2在肾脏皮质迷路的远曲小管和皮、髓质交界处的弓形动脉壁平滑肌呈强阳性表达(+++),在髓质的远直小管呈弱阳性表达(+),此外,在肾脏组织其它区域中未见EP2阳性表达。结论 EP2在猕猴肾远曲小管、弓形动脉壁平滑肌和远直小管中有表达,提示EP2这种分布特征与肾功能相关。
Objective To investigate the expression and distribution of prostaglandin E2 receptor EP2 in the renal tissues of normal Macaca fascicularis and to explore the correlation between the distribution of EP2 and renal function. Methods The prepared renal paraffin sections of Macaca fascicularis were used,to identify the renal tissue structure by HE staining. Immunohistochemical SP method was used to observe the immuno-positive expression of EP2 in the kidney. The HP IAS1000 high-definition image analysis system was then used to observe and collect images of the HE staining and immunohistochemistry results. Results The immuno-positive product of EP2 was brown, the distribution and the intensity of expression differed in various areas of the kidney.Immunohistochemistry results showed that EP2 was strongly positively expressed in the distal convoluted tubules in the cortical labyrinth and smooth muscle of the arcuate wall in the junction of the renal cortex(+++),while it was weakly positively in the distal straight tubules in renal medulla(+). No positive expression of EP2 was observed in other structures of renal areas. Conclusion EP2 is expressed in the distal convoluted tubules, distal straight tubules and the smooth muscle of the arcuate wall in the kidney of Macaca fascicularis, which suggesting that the distribution of EP2 is related to renal function.
Objective To investigate the expression and distribution of prostaglandin E2 receptor EP2 in the renal tissues of normal Macaca fascicularis and to explore the correlation between the distribution of EP2 and renal function. Methods The prepared renal paraffin sections of Macaca fascicularis were used,to identify the renal tissue structure by HE staining. Immunohistochemical SP method was used to observe the immuno-positive expression of EP2 in the kidney. The HP IAS1000 high-definition image analysis system was then used to observe and collect images of the HE staining and immunohistochemistry results. Results The immuno-positive product of EP2 was brown, the distribution and the intensity of expression differed in various areas of the kidney.Immunohistochemistry results showed that EP2 was strongly positively expressed in the distal convoluted tubules in the cortical labyrinth and smooth muscle of the arcuate wall in the junction of the renal cortex(+++),while it was weakly positively in the distal straight tubules in renal medulla(+). No positive expression of EP2 was observed in other structures of renal areas. Conclusion EP2 is expressed in the distal convoluted tubules, distal straight tubules and the smooth muscle of the arcuate wall in the kidney of Macaca fascicularis, which suggesting that the distribution of EP2 is related to renal function.
引文
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[16] MORATH R,KLEIN T,SEYBERTH H W,et al. Immunolocalization of the four prostaglandin E2 receptor proteins EP1,EP2,EP3,and EP4 in human kidney[J]. J Am Soc Nephrol,1999,10(9):1851-1860.
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[19]SRIVASTAVA T,ALON U S,CUDMORE P A,et al. Cyclooxygenase-2,prostaglandin E2,and prostanoid receptor EP2 in fluid flow shear stress-mediated injury in the solitary kidney[J]. Am J Physiol Renal Physiol,2014,307(12):F1323-1333.
[20] TILLEY S L,AUDOLY L P,HICKS E H,et al. Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E2 receptor[J]. J Clin Invest,1999,103(11):1539-1545.
[21] KENNEDY C R,ZHANG Y,BRANDON S,et al.Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor[J]. Nat Med,1999,5(2):217-220.
[22] HOHJOH H, INAZUMI T, TSUCHIYA S, et al.Prostanoid receptors and acute inflammation in skin[J].Biochimie,2014,107(Pt A):78-81.
[2] KIDA T,SAWADA K,KOBAYASHI K,et al. Diverse effects of prostaglandin E2 on vascular contractility[J].Heart Vessels,2014,29(3):390-395.
[3] KAWAHARA K,HOHJOH H,INAZUMI T,et al.Prostaglandin E2-induced inflammation:Relevance of prostaglandin E receptors[J]. Biochim Biophys Acta,2015,1851(4):414-421.
[4] MARKOVIC T,JAKOPIN Z,DOLENC M S,et al. Structural features of subtype-selective EP receptor modulators[J]. Drug Discov Today,2017,22(1):57-71.
[5]郭小兵,吴德野,李恒希,等.一种轻型脑损伤后大鼠海马EP2的表达变化[J].昆明医科大学学报,2017,38(4):5-9.
[6] LUO X,ZHU Q,ZHANG J,et al. The double roles of the prostaglandin E2 EP2 receptor in intracerebral hemorrhage[J]. Curr Drug Targets,2017,18(12):1377-1385.
[7] ROJAS A,GANESH T,LELUTIU N,et al. Inhibition of the prostaglandin EP2 receptor is neuroprotective and accelerates functional recovery in a rat model of organophosphorus induced status epilepticus[J]. Neuropharmacology,2015,93(1):15-27.
[8] LI P,JIANG H,WU H,et al. AH6809 decreases production of inflammatory mediators by PGE2-EP2-c AMP signaling pathway in an experimentally induced pure cerebral concussion in rats[J]. Brain Res,2018,1698(4):11-28.
[9]蒋鸿雁,吴海鹰,吴德野,等. EP2受体抑制剂AH6809对单纯性脑震荡大鼠皮质中肿瘤坏死因子表达的调控[J].神经解剖学杂志,2018,34(4):441-446.
[10] FUWA M,TORIS C B,FAN S,et al. Effects of a novel selective EP2 receptor agonist,omidenepag isopropyl,on aqueous humor dynamics in laser-Induced ocular hypertensive monkeys[J]. J Ocul Pharmacol Ther,2018,34(7):531-537.
[11] KIRIHARA T,TANIGUCHI T,YAMAMURA K,et al.Pharmacologic characterization of omidenepag isopropyl,a novel selective EP2 receptor agonist,as an ocular hypotensive agent[J]. Invest Ophthalmol Vis Sci,2018,59(1):145-153.
[12] VUKICEVIC S,SIMIC P,BOROVECKI F,et al. Role of EP2 and EP4 receptor-selective agonists of prostaglandin E(2)in acute and chronic kidney failure[J]. Kidney Int,2006,70(6):1099-1106.
[13]JENSEN B L,STUBBE J,HANSEN P B,et al. Localization of prostaglandin E(2)EP2 and EP4 receptors in the rat kidney[J]. Am J Physiol Renal Physiol,2001,280(6):F1001-1009.
[14]GUAN Y,STILLMAN B A,ZHANG Y,et al. Cloning and expression of the rabbit prostaglandin EP2 receptor[J].BMC Pharmacol,2002,2(1):14.
[15]贾晓辉,孔令喆,王先火,等. 32例套细胞淋巴瘤中BTK蛋白的表达及临床意义[J].中国肿瘤临床,2017,44(19):963-968.
[16] MORATH R,KLEIN T,SEYBERTH H W,et al. Immunolocalization of the four prostaglandin E2 receptor proteins EP1,EP2,EP3,and EP4 in human kidney[J]. J Am Soc Nephrol,1999,10(9):1851-1860.
[17]BREYER M D,DAVIS L,JACOBSON H R,et al. Differential localization of prostaglandin E receptor subtypes in human kidney[J]. Am J Physiol, 1996, 270(2):F912-918.
[18] BREYER M D,JACOBSON H R,BREYER R M. Functional and molecular aspects of renal prostaglandin receptors[J]. J Am Soc Nephrol,1996,7(1):8-17.
[19]SRIVASTAVA T,ALON U S,CUDMORE P A,et al. Cyclooxygenase-2,prostaglandin E2,and prostanoid receptor EP2 in fluid flow shear stress-mediated injury in the solitary kidney[J]. Am J Physiol Renal Physiol,2014,307(12):F1323-1333.
[20] TILLEY S L,AUDOLY L P,HICKS E H,et al. Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E2 receptor[J]. J Clin Invest,1999,103(11):1539-1545.
[21] KENNEDY C R,ZHANG Y,BRANDON S,et al.Salt-sensitive hypertension and reduced fertility in mice lacking the prostaglandin EP2 receptor[J]. Nat Med,1999,5(2):217-220.
[22] HOHJOH H, INAZUMI T, TSUCHIYA S, et al.Prostanoid receptors and acute inflammation in skin[J].Biochimie,2014,107(Pt A):78-81.