目的 通过构建被动型 Heymann 肾炎(passive Heymann nephritis, PHN)大鼠模型,观察石榴皮鞣质对PHN大鼠肾组织足细胞nephrin和podocin表达的影响。方法 将健康雄性SD大鼠随机分为6组(n=6):假手术组、模型组、贝那普利组(10 mg·kg-1)、石榴皮鞣质高、中、低剂量组(60, 40, 20 mg·kg-1)。造模成功后,每天灌胃给药1次,直至第5周处死大鼠,取肾脏,免疫组化法检测转化生长因子-β1(TGF-β1)和C3的表达,免疫荧光检测IgG的沉积情况,RT-PCR和Western blot法检测足细胞nephrin 和podocin mRNA及蛋白表达情况。结果 实验结果显示,与假手术组相比,模型组大鼠TGF-β1和C3表达显著性增多,IgG在肾组织中的沉积也显著性增加,且nephrin和podocin的mRNA及蛋白表达明显降低;与模型组相比,贝那普利组和石榴皮鞣质各剂量组TGF-β1和C3表达显著性降低,IgG的沉积得到改善,nephrin和podocin mRNA及蛋白表达明显升高。结论 石榴皮鞣质对被动型 Heymann 肾炎大鼠有较好的治疗作用。
Abstract
OBJECTIVE To observe the effect of tannins from Punica granatum L (TPG) on the expression of nephrin and podocin in podocytes of kidney of rats with passive Heymann nephritis (PHN). METHODS Healthy male Sprague-Dawley rats were randomly divided into six groups (n=6): sham group, model group, benazepril group (10 mg·kg-1), and TPG groups respectively at high, medium and low dose (60, 40, 20 mg·kg-1). After the success of modeling of PHN, the rats were intragastrically administered once a day for 5 weeks. At the end of the experiment, the rats were sacrificed, and the kidney was taken. The expression of transforming growth factor-β1 (TGF-β1) and C3 was detected by immunohistochemistry, and the deposition status of IgG was detected by immunofluorescence. RT-PCR and Western blot were used to detect the expression of nephrin and podocin mRNA and proteins in podocytes. RESULTS Compared with the sham group, the expression of TGF-β1 and C3 in the model group was significantly increased, the deposition of IgG in the renal tissue was also significantly increased, and the expression of nephrin and podocin mRNA and protein was significantly decreased. As compared with the model group, the expression of TGF-β1 and C3 was significantly decreased in each dose group of TPG and benazepril, the deposition of IgG was decreased, and the expression of nephrin, podocin mRNA and proteins was significantly increased. CONCLUSION TPG has obvious therapeutic effects on passive Heymann nephritis rats.
关键词
石榴皮 /
鞣质 /
Heymann 肾炎 /
nephrin /
podocin
{{custom_keyword}} /
Key words
Punica granatum L /
tannins /
Heymann nephritis /
nephrin /
podocin
{{custom_keyword}} /
中图分类号：
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] LIU T T, WANG Y Y, ZHAN Y L. TCM treatment ideas and methods for membranous nephropathy [J]. Glob Tradit Chin Med (环球中医药), 2019, 12(10):1555-1557.
[2] NI R T, YANG Q F. Research progress on experimental animal models of chronic nephritis [J]. J Med Res (医学研究杂志), 2014, 43(1):145-148.
[3] WANG X F, XU Y Q, LI C X, et al. Research progress of traditional Chinese medicine in the treatment of nephrotic syndrome [J]. Guid J Tradit Chin Med Pharm (中医药导报), 2018, 24(11):100-103,116.
[4] Ch.P(2015) VolⅠ(中国药典2015年版. 一部)[S]. 2015:93-94.
[5] LI Q L, TU J, ZHOU B H. The tannins from Punica granatum L, natural regulator of TGF-β1/Smad signaling activity improves nephrectomy and adriamycin induced focal segmental glomerulosclerosis in vivo [J]. J Funct Foods, 2019, 57:361-372.
[6] ZHOU B H, GUO Z L, WANG H Y, et al. Protective effect of tannin in Punica granatum L. on chronic renal failure in rats induced by adenin [J]. Chin Pharm J (中国药学杂志), 2009, 44(22): 1699-1703.
[7] ZHOU B H, ZHOU J, LIANG Y X, et al. Study on effect of tannins in Granati Pericarpium on renal fibrosis in rats [J]. Chin Tradit Herb Drugs (中草药), 2014,45(11): 1585-1590.
[8] ZHANG L, HUANG W X, CHENG J G. Effect of different doses of anti-Fx1A on passive Heymann nephritis model in rats [J]. Chin J Integr Tradit West Nephrol (中国中西医结合肾病杂志),2018,19(12):1052-1054.
[9] GUO Z L, FAN J, WEI Y, et al. Study on the protective effect of tannin in Punica granatum L. on rats with nephrotic syndrome induced by adriamycin [J]. Chin J Hosp Pharm (中国医院药学杂志),2010,30(20):1722-1724.
[10] CATTRAN D C, KIM E D, REICH H, et al. Membranous nephropathy: quantifying remission duration on outcome [J]. J Am Soc Nephrol, 2017, 28(3):995-1003.
[11] WANG L Y, HONG Q, LV Y, et al. Autophagy can repair endoplasmic reticulum stress damage of the passive Heymann nephritis model as revealed by proteomics analysis [J]. J Proteomics, 2012, 75: 3866-3876.
[12] ZHOU B H, ZHOU J, GUO X X, et al. Effect of tannins from Pomegranate Rind on passive Heymann nephritis in rats [J]. Chin Pharm (中国药师),2015, 18(10):1629-1633.
[13] LÓPEZ-HERNÁNDEZ F J, LÓPEZ-NOVOA J M. Role of TGF-β in chronic kidney disease: an integration of tubular, glomerular and vascular effects [J]. Cell Tissue Res, 2012, 347:141-154.
[14] LIU Y. New insights into epithelial-mesenchymal transition in kidney fibrosis[J]. J Am Soc Nephrol, 2010, 21:212-222.
[15] GOUD M P, BALE S, PULIVENDALA G, et al. Therapeutic effects of nimbolide, an autophagy regulator, in ameliorating pulmonary fibrosis through attenuation of TGF-beta1 driven epithelial-to-mesenchymal transition[J]. Int Immunopharmacol, 2019, 75:105755.
[16] MENG X M. Inflammatory mediators and renal fibrosis [J]. Adv Exp Med Biol, 2019, 1165: 381-401.
[17] GLASSOCK R J. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey [J]. Am J Kidney Dis, 2010, 56: 157-167.
[18] TANG Z, LU B, HATHCH E, et al. C3a mediates epithelial-to-mesenchymal transition in proteinuric nephropathy [J]. J Am Soc Nephrol, 2009, 20(3): 593-603.
[19] LIU H Q, FAN Y P, DA Z Y, et al. Expression changes of nephrin and podocin in patients with membranous nephropathy [J]. Chin J Nephrol Dialysis Transplant (肾脏病与透析肾移植杂志), 2009, 18(4): 318-328.
[20] KAWCHI H, MIYAUCHI N, SUZUKI K, et al. Role of podocyte slit diaphragm as a filtration barrier [J]. Nephrol, 2006, 11(4): 274-281.
[21] PATRAKKA J, TRYGGYASON K. Nephrin-a unique structural and signaling protein of the kidney filter [J]. Trend Mol Med, 2007, 13(9): 396-403.
[22] JONNSTONE D B, HOLZMAN L B. Clinical impact of research on the podocyte slit diaphragm [J]. Nat Clin Pract Nephrol, 2006, 2(5): 271-282.
[23] CHEN Y, LIN L, TAO X, et al. The role of podocyte damage in the etiology of ischemia-reperfusion acute kidney injury and post-injury fibrosis [J]. BMC Nephrol, 2019,20:106.
[24] RUGGENENTI P, TRILLINI M, BARLOVIC D P, et al. Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: a prospective, randomized, controlled trial [J]. Diabetes Obes Metab, 2019,21(5): 1177-1190.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金项目资助(31170330)
{{custom_fund}}
PDF(3364 KB)
