小分子多肽化合物CMS001对肾性贫血的治疗作用及机理研究
摘要
目的:
研究十肽化合物CMS001对肾性贫血(Renal Anemia)治疗作用,并初步探讨其可能的作用机制。
方法:
1.选用雄性Wistar大鼠,建立腺嘌呤和5/6肾切除两种大鼠肾性贫血动物模型,观察CMS001 80μg/kg/d组、40μg/kg/d组、20μg/kg/d组对大鼠血常规、肾功能的影响。
2.应用HE染色法观察CMS001对肾性贫血大鼠肾组织病理改变的影响。
3.应用Western Blot方法观察CMS001对肾性贫血大鼠肾组织中EPO蛋白表达水平的影响。
4.应用RT-PCR方法观察CMS001对肾性贫血大鼠肾组织中EPO mRNA水平的影响。
结果:
1.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001可以明显改善肾性贫血大鼠外周血中红细胞、血红蛋白和红细胞压积的水平,与生理盐水组比较,差异有统计学意义(P＜0.05);CMS001还可以明显降低肾性贫血大鼠血清中肌酐、尿素氮水平,与生理盐水组比较,差异有统计学意义(P＜0.05)。
2.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001能明显改善大鼠肾组织的肾小管扩张和变性坏死,减少炎性细胞的浸润,降低肾间质的纤维化程度。
3.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001能增加肾性贫血大鼠肾脏组织中EPO的蛋白表达水平,与生理盐水组比较有显著性差异(P＜0.05)。
4.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001能增加肾性贫血大鼠肾脏组织中EPO mRNA水平,与生理盐水组比较有显著性差异(P＜0.05)。
结论:
CMS001能够上调肾脏组织中EPO mRNA水平和EPO蛋白表达水平,增加外周血中红细胞、血红蛋白和红细胞压积的水平,使血清尿素氮、肌酐下降,改善肾组织的病理损伤,延缓肾功能损害进展,纠正贫血状态。
Objective:
To investigate the therapeutic effect of decapeptide CMS001 on Renal Anemia and its possible mechanisms.
Methods:
1.Two kinds of animal model were used to investigate the therapeutic effect of decapeptide CMS001 on Renal Anemia.The one was adenine of intragastric administration to the Wistar rats,and the other was 5/6 nephrectomy on rats.The therapeutical effect of CMS001(80μg/kg/d,40μg/kg/d,20μg/kg/d)on peripheral hemogram and renal function of renal anemia rats were observed.
2.HE stain was used to observe the therapeutical effect of CMS001 on pathological damage of kidney of RA rats.
3.The effect of CMS001 on EPO protein level in the kidney of RA rats was assayed by Western Blot methods.
4.The effect of CMS001 on EPO mRNA level in the kidney of RA rats was assayed by Real-time PCR methods.
Results:
1.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can significantly increase sum total of erythrocyte,hemoglobin and hematocrit in the peripheral blood of RA rats (P＜0.05).CMS001 also can significantly decrease serum BUN and Scr of RA rats (P＜0.05).
2.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can ameliorate the kidney pathological damage of RA rats.
3.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can remarkably increase EPO protein expression level in the kidney of RA rats(P＜0.05).
4.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can remarkably increase EPO mRNA level in the kidney of RA rats(P＜0.05).
Conclusions:
Decapeptide CMS001 has the therapeutic effect on RA rats.CMS001 can remarkably increase protein expression level and EPO mRNA level in the kidney of RA rats.CMS001 can significantly increase sum total of erythrocyte,hemoglobin and hematocrit in the peripheral blood and decrease serum BUN and Scr of RA rats. CMS001 can ameliorate the kidney pathological damage of RA rats.
研究十肽化合物CMS001对肾性贫血(Renal Anemia)治疗作用,并初步探讨其可能的作用机制。
方法:
1.选用雄性Wistar大鼠,建立腺嘌呤和5/6肾切除两种大鼠肾性贫血动物模型,观察CMS001 80μg/kg/d组、40μg/kg/d组、20μg/kg/d组对大鼠血常规、肾功能的影响。
2.应用HE染色法观察CMS001对肾性贫血大鼠肾组织病理改变的影响。
3.应用Western Blot方法观察CMS001对肾性贫血大鼠肾组织中EPO蛋白表达水平的影响。
4.应用RT-PCR方法观察CMS001对肾性贫血大鼠肾组织中EPO mRNA水平的影响。
结果:
1.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001可以明显改善肾性贫血大鼠外周血中红细胞、血红蛋白和红细胞压积的水平,与生理盐水组比较,差异有统计学意义(P＜0.05);CMS001还可以明显降低肾性贫血大鼠血清中肌酐、尿素氮水平,与生理盐水组比较,差异有统计学意义(P＜0.05)。
2.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001能明显改善大鼠肾组织的肾小管扩张和变性坏死,减少炎性细胞的浸润,降低肾间质的纤维化程度。
3.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001能增加肾性贫血大鼠肾脏组织中EPO的蛋白表达水平,与生理盐水组比较有显著性差异(P＜0.05)。
4.给药剂量为80μg/kg/d、40μg/kg/d时,CMS001能增加肾性贫血大鼠肾脏组织中EPO mRNA水平,与生理盐水组比较有显著性差异(P＜0.05)。
结论:
CMS001能够上调肾脏组织中EPO mRNA水平和EPO蛋白表达水平,增加外周血中红细胞、血红蛋白和红细胞压积的水平,使血清尿素氮、肌酐下降,改善肾组织的病理损伤,延缓肾功能损害进展,纠正贫血状态。
Objective:
To investigate the therapeutic effect of decapeptide CMS001 on Renal Anemia and its possible mechanisms.
Methods:
1.Two kinds of animal model were used to investigate the therapeutic effect of decapeptide CMS001 on Renal Anemia.The one was adenine of intragastric administration to the Wistar rats,and the other was 5/6 nephrectomy on rats.The therapeutical effect of CMS001(80μg/kg/d,40μg/kg/d,20μg/kg/d)on peripheral hemogram and renal function of renal anemia rats were observed.
2.HE stain was used to observe the therapeutical effect of CMS001 on pathological damage of kidney of RA rats.
3.The effect of CMS001 on EPO protein level in the kidney of RA rats was assayed by Western Blot methods.
4.The effect of CMS001 on EPO mRNA level in the kidney of RA rats was assayed by Real-time PCR methods.
Results:
1.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can significantly increase sum total of erythrocyte,hemoglobin and hematocrit in the peripheral blood of RA rats (P＜0.05).CMS001 also can significantly decrease serum BUN and Scr of RA rats (P＜0.05).
2.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can ameliorate the kidney pathological damage of RA rats.
3.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can remarkably increase EPO protein expression level in the kidney of RA rats(P＜0.05).
4.At the dose of 80μg/kg/d,40μg/kg/d,CMS001 can remarkably increase EPO mRNA level in the kidney of RA rats(P＜0.05).
Conclusions:
Decapeptide CMS001 has the therapeutic effect on RA rats.CMS001 can remarkably increase protein expression level and EPO mRNA level in the kidney of RA rats.CMS001 can significantly increase sum total of erythrocyte,hemoglobin and hematocrit in the peripheral blood and decrease serum BUN and Scr of RA rats. CMS001 can ameliorate the kidney pathological damage of RA rats.
引文
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[2]叶任高,刘冠贤.临床肾脏病学,人民卫生出版社[M],第1版,1997,243.
[3]Eckardt KU.Pathophysiology of renal anemia.Clin Nephol[J],2000,53(1 Suppl):S2-8.
[4]Gouva C,Nikolopoulos P,et al.Kidney Int[J],2004,66(2):753-60.
[5]Elliott S,Lorenzini T,Asher S,et al.Nature Biotechnol[J],2003,21(4):414-421.
[6]Wrighton NC,Farrell FX,Chang R,et al.Small peptide as potent mimetics of the proteinlform one erythropoietin.Science[J],1996,273(2):458-463.
[7]杜晓霞.国外医学移植与血液净化分册[J],2004,2(3):1-4.
[8]Kelly W.Therapeutic peptides:the devil is in the details.Bio Technol[J].1996;14(1):28-31.
[9]Wang L,Zhang HL,et al.The decapeptide CMS001 enhances swimming endurance in mice.Peptides[J].2008 Mar 13.
[10]董德长.实用肾脏病学tM].上海:上海科学技术出版社[M],1999.751-752.
[11]郑东平,朱燕俐,丁名城,等.用腺嘌呤制作慢性肾功能衰竭动物模型[J].中华肾脏病杂志,1989,5(5):342.
[12]Yokozawa T,Zheng PD,Oura H,et al.Animal model of adenine induced chronic renal failure in rats.Nephron,1986,44(3):230-234.
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