和肾络对5/6肾切除大鼠肾组织增殖细胞核抗原、细胞间黏附分子-1表达影响的研究
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摘要
目的：研究和肾络治疗5/6肾切除慢性肾功能衰竭模型大鼠肾组织增殖细胞核抗原(PCNA)及黏附分子-1(ICAM-1)表达的影响,探讨其对肾纤维化的保护作用。方法：采用5/6肾切除模型大鼠,设立正常组、模型组、西药福辛普利组、中药低剂量组、中剂量组及高剂量组。检测各组24 h尿蛋白定量,血清尿素氮(BUN)、血清肌酐(SCr)、总蛋白(TP)、白蛋白(Alb)、甘油三酯(TG)、胆固醇(TC)、低密度脂蛋白(LDI)、高密度脂蛋白(HDL)、血红蛋白(HB)水平,取残肾组织行HE染色,光镜观察肾组织病理变化,免疫组化检测肾增殖细胞核抗原(PCNA)及黏附分子-1(ICAM-1)的变化。结果：中药组与福辛普利治疗组24小时尿蛋白排泄量、BUN.Scr.血脂水平明显低与模型组,中药中剂量与高剂量组提高白蛋白及血红蛋白优于福辛普利组；增殖细胞核抗原与细胞间黏附因子-1术后表达较正常组升高,用药组表达明显低与模型组。结论：1.和肾络可明显减少5/6肾切除大鼠的尿蛋白排泄量、纠正贫血及脂代谢紊乱,降低血肌酐和尿素氮,改善肾功能,改善肾组织的病理损伤,能够保护残存肾单位,延缓肾纤维化的进展。2.抑制PCNA与ICAM-1在肾组织内的过度表达；延缓肾脏纤维化的过程。
Objective:To study the expression of proliferating cell nuclearantigen(PCNA) and intercellular adhesion molecule-1 (ICAM-1) changes of 5/6 nephrectomy rats, which to explore the mechanism of renal fibrosis and the mechanism of Heshenluo on renal fibrosis protection. Methods:Using 5/6 nephrectomy rats divided into 5 groups, which are normal group, model group, treated by Fuxinpuli group, treated by Heshenluo Low-dose group, Heshenluo middle-dose group and High-dose group. Urinary protein excretion for 24 hours, blood urea nitrogen(BUN), serum creatinine(Scr), total plasma protein (TP), hemoglobin(Hb), plasma albumin(ALB), triglyceride(TG), cholesterol(CHO), high density lipoprotein(HDL), low density lipoprotein(LDL). Take the renal tissue from the operative side. HE staining and immunohistochemical methods were used to detect the changes of proliferating cell nuclearantigen(PCNA), intercellular adhesion molecule-] (ICAM-1). Results: Compared with the untreated 5/6 nephrectomized group, Urinary protein, BUN, SCr, TG. TC, LDL of Heshenluo groups and Fuxinpuli group were substantially decreased(P< 0.05). Heshenluo middle-dose group and High-dose group was better in increasing ALB and HB than Fuxinpuli group. The expression of proliferating cell nuclearantigen(PCNA), intercellular adhesion molecule-1 (ICAM-1) in 5/6 nephrectomy rats is higher than in normal group. It was less in Heshenluo groups and Fuxipuli group. Conclusion:1 The Heshenluo can decrease the loss of rat's urine protein and the production of BUN, SCr, TG, TC, LDL, increasing ALB and HB, protect the renal function, improve the pathological lesion of renal tissue, protect the remaining nephron, retard renal fibrosis.2 Inhibit the excessive expression of proliferating cel nuclearantigen(PCNA), intercellular adhesion molecule-1 (ICAM-1), retard renal fibrosis.
Objective:To study the expression of proliferating cell nuclearantigen(PCNA) and intercellular adhesion molecule-1 (ICAM-1) changes of 5/6 nephrectomy rats, which to explore the mechanism of renal fibrosis and the mechanism of Heshenluo on renal fibrosis protection. Methods:Using 5/6 nephrectomy rats divided into 5 groups, which are normal group, model group, treated by Fuxinpuli group, treated by Heshenluo Low-dose group, Heshenluo middle-dose group and High-dose group. Urinary protein excretion for 24 hours, blood urea nitrogen(BUN), serum creatinine(Scr), total plasma protein (TP), hemoglobin(Hb), plasma albumin(ALB), triglyceride(TG), cholesterol(CHO), high density lipoprotein(HDL), low density lipoprotein(LDL). Take the renal tissue from the operative side. HE staining and immunohistochemical methods were used to detect the changes of proliferating cell nuclearantigen(PCNA), intercellular adhesion molecule-] (ICAM-1). Results: Compared with the untreated 5/6 nephrectomized group, Urinary protein, BUN, SCr, TG. TC, LDL of Heshenluo groups and Fuxinpuli group were substantially decreased(P< 0.05). Heshenluo middle-dose group and High-dose group was better in increasing ALB and HB than Fuxinpuli group. The expression of proliferating cell nuclearantigen(PCNA), intercellular adhesion molecule-1 (ICAM-1) in 5/6 nephrectomy rats is higher than in normal group. It was less in Heshenluo groups and Fuxipuli group. Conclusion:1 The Heshenluo can decrease the loss of rat's urine protein and the production of BUN, SCr, TG, TC, LDL, increasing ALB and HB, protect the renal function, improve the pathological lesion of renal tissue, protect the remaining nephron, retard renal fibrosis.2 Inhibit the excessive expression of proliferating cel nuclearantigen(PCNA), intercellular adhesion molecule-1 (ICAM-1), retard renal fibrosis.
引文
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[45]黄杰雄.增殖细胞核抗原的研究进展.国外医学生理、病理科学与临床分册,1994,14(1)：9—11.
[46]陈香美,喻陆,徐启河.肾脏细胞的活化与慢性进展性肾病.中华肾脏病杂 志,2000.16：52-54.
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[2]Riser BL, Varani J, Cortes P, et al. Cyclic stretching of mesangial cells up-regulates intercellular adhesion molecul-1 and leukotgte adherente:a possible new mechanism for glomerulosclerosis.Am J Pathol,2001,158(1):11-17.
[3]王蔚,樊均明,陈辉珍.5/6肾切除大鼠肾组织CD44和CD54的变化及阿魏酸钠和氯沙坦的干预作用.中国中西医结合肾病杂志,2005,6(5)：285-287.
[4]Raij L, Azar S, Keane W. Mexangia immune injury, hypertension, and progessiv glomerular damage in Dahl rats.Kidney Int,1984,26:137-143.
[5]杜胜华,唐德焱,陈孝文.细胞因子、肾间质细胞与肾间质纤维化.国外医学泌尿系统分册,2004,24(1)：93-97.
[6]Shimamura T,Nakamura K.A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats[J]. Am J Pathol,1975,79:9597
[7]Gretz N, Floege J, Sugenoya Y,et al. Nutri tional treatment of CRF [J]. AM J Nephrol,1989,61:147150.
[8]Sterner G, Wennberg A.Partial nephrectomy and chronic renal failure, the"adult"rat model[J]. Contr Nephrol,1988,60:3940.
[9]Ritz E, Furst P, Yoshimura A. The role of the parathroid glands in the uremic syndrome[J].Am J Kidney Dis,1995,26;(5):808-811.
[10]沈延春,杨晓,陈琼霞.5/6肾切除大鼠肾脏病理学动态变化[J].上海实验动物科学,2005,25(1)：21-24.
[11]Barata K, Yoshida M, Hokao R,et al.Function in 5/6 nephrectomized ratsbasic study for renal toxicity using 5/6 nephrectomized rats[J]. J Toxicol Sci,1998,23 (5): 433-442.
[12]袁发焕,史景泉,光丽霞,等.残肾肾小球毛细血管增生及其意义的实验研究[J].中国体视学与图像分析,1997,2(4)：249-252.
[13]于俊生编著.中西医结合诊治水肿与积液,北京：科学技术文献出版社1997；33.
[14]李如辉.危机、危机的化解与新生.浙江中医学院学报,1999；23(4)：1.
[15]周恩超,曾安平,王钢.从痰论治慢性肾衰竭.长春中医药大学学报,2007,23(4)：35-36.
[16]于俊生.痰瘀相关学说与疑难病治疗[M].北京：人民卫生出社,2008：35-37.
[17]许筱颖,郭霞珍.浊毒致病理论初探.辽宁中医药杂志,2007,34(1)：28-29.
[18]于俊生.痰瘀相关学说与临床[M].北京：科学技术文献出版社,1995：32.
[19]黄春林,朱晓新.中药药理与临床手册,北京：人民卫生出版社,2006,第一版：653.
[20]朱陵群,黄启福,魏明,等.川芎嗪对于家兔模型肾炎时血小板活性的影响.中国病理生理杂志,1995；11(4)：382-386.
[21]张雪静,黄秀兰,王伟.土茯苓抑制白介素-1诱导的血管内皮细胞细胞间黏附分子-1的表达.中国医药学报,2004,19(6)：344-346.
[22]关美君,张吉德,丁源.我国海洋湖沼药物科学研究进度[J].内部资料,1991.1.
[23]陈淑梅,李领华,何志坚.甘糖酯对大鼠血小板聚集和大鼠与家免实验性血栓形成的影响[J].中国海洋药物,1990,,9(4)：4.
[24]邓槐春,谈竞光,谢姣蛾,等.海带多糖对血脂血症的临床疗效初步观察[J].中草药,1987,18(8)：12.
[25]张融端,华一俐,冯群光.昆布不同溶剂提取物的降脂实验[J].南京中医学院学报,1988(4)：57.
[26]侯毓礼.海带根药理实验研究[J].中草药,1984,15(12)：19.
[27]远方,叶任高.叶任高治疗慢性肾功能衰竭经验集要.辽宁中医杂志.2001,28(6)：336-337.
[28]魏向阳.大黄延缓慢性肾功能衰竭机制的研究进展.现代中医药.2003,3：58-59.
[29]张逸凡,于庆海.淫羊藿总黄酮的免疫调节作用.沈阳药科大学学报.1999,16(3)：182-184.
[30]武敬亮,张璟霞,苏智先,等.淫羊藿研究新进展.中医药学报,2004,32(3)：69-72.
[31]李晓,周李同,吴佩,等.大鼠输尿管梗阻后肾炎中的P选择素表达及意义[J].上海第二医科大学学报,2000,20(5)：399—401.
[32]孙桂芝,周同,吴开胤,等.树突状细胞在大鼠单侧输尿管梗阻后肾组织中的分布与作用[J].上海第二医科大学学报,2004,24(3)：174-177.
[33]Lange—-Sperandio B, Caehat F, Thornhill BA. Selectis mediate Macrophage infiltration in obstructive nephropathy in newhorn mice[J].Kidney Int 2002,61 (2):516-524.
[34]黄岚.细胞间黏附分子1与心功能不全的临床意义[J].国外医学心血管疾病分册,2000,27(1)：5-7.
[35]王惠娟.细胞间黏附分子与缺血性卒中[J].脑与神经疾病杂志,2001,9(1)：封3-4.
[36]Yokoyama H, Tomosugi N, Takaeda M et al.[J] Am Soc Nephrol, 1992;3:669(Abstr).
[37]Bruijn JA, Dinklo NJCM.Lab Invest,1993;69(3):329-335
[38]Patey N, Lesavre P, Halbwachs L et al[J], Pathol,1996; 179:414-420
[39]Kawasaki K, Yaeita E, Yamamoto T et al[J], Immunol, 1993; 150(3):1074-108.
[40]Inoue H, Saito I, Nakazawa R et al·Nephrol DialTrans-plant,1995; 10:2077-2082
[41]Cosmi AB, Conti D, Delmonico FL et al[J] Immunol,1990; 144:4604-4612
[42]Haug CE, Colvin RB, Delmonico FL et al·Transplantation,1993;55:766-77
[43]Aderson JA, Lentsch AB, Hadjiminas DJ,et al. The role of cytokines, adhesion molecules, chemokines in interleukin-2 induced lymphocytic infiltration in C57BL/6 mice. JClin Invest.1996,87:1952.
[44]el Nahas AM, Muchaneta-Kubara EC, Essawy M, et al. Renal fibrosis:insights into pathogenesis and treatment. Int J Biochem Cell Biol 1997,29(1):55-62.
[45]黄杰雄.增殖细胞核抗原的研究进展.国外医学生理、病理科学与临床分册,1994,14(1)：9—11.
[46]陈香美,喻陆,徐启河.肾脏细胞的活化与慢性进展性肾病.中华肾脏病杂 志,2000.16：52-54.
[47]Floege J etal. Kldney Int,1991,40:477-488.
[48]Floege J, Burns MW. Alpers CE, et al. Glomerular cell pro-liferation and PDGF expression precede glomerulosclerosis in the remnant kidney model. Kidney Int 1992,41(2):297-309.
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