氢氧化镧对大鼠慢性肾衰高磷血症的改善作用研究
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摘要
目的:研究氢氧化镧对大鼠慢性肾衰高磷血症的改善作用。方法:取大鼠建立慢性肾衰高磷血症模型,再随机分为模型组、碳酸镧组[0.3 g/(kg·d)]、碳酸钙组[4.2 g/(kg·d)]和氢氧化镧高、中、低剂量组[1.5、1、0.5 g/(kg·d)],每组10只。同日上午继续ig腺嘌呤0.2 g/(kg·d),下午ig相应药物,1周后停止给予腺嘌呤,连续给药22 d,另取10只正常大鼠作为正常对照组。对各组小鼠进行一般检查,末次给药后检测大鼠肾脏系数,血清中钙、磷、甲状旁腺素(PTH)、肌酐、尿素氮含量,以及肾脏病理学变化。结果:与正常对照组比较,模型组大鼠呈现慢性肾衰体征,肾脏系数和磷、PTH、肌酐、尿素氮含量均增加,钙含量减少(P<0.01),肾脏切片呈明显病理学特征。与模型组比较,碳酸镧组、碳酸钙组和氢氧化镧各剂量组大鼠慢性肾衰体征均改善,肾脏系数(除氢氧化镧高剂量组外)和磷(除碳酸钙组外)、PTH(除氢氧化镧低剂量组、碳酸钙组外)、肌酐(除氢氧化镧低剂量组、碳酸钙组外)、尿素氮含量均减少,钙含量和钙磷乘积(仅碳酸钙组)均增加(P<0.05或P<0.01),其余差异无统计学意义;肾脏切片病理学特征好转。结论:氢氧化镧可改善慢性肾衰高磷血症模型大鼠肾功能,降低血清磷含量。
OBJECTIVE:To study the improvement effect of lanthanum hydroxide on chronic renal failure(CRF)hyperphosphatemia in rats. METHODS:CRF hyperphosphatemia rat model were induced and then randomly divided into model group,lanthanum carbonate group [0.3 g/(kg·d)],calcium carbonate group [4.2 g/(kg·d)] and lanthanum hydroxide high-dose,medium-dose and low-dose groups [1.5,1,0.5 g/(kg·d)] with 10 rats in each group. They were given adenine 0.2 g/(kg·d)intragastrically in the morning,and then given relevant medicine intragastrically in the afternoon;a week later,they stopped taking adenine but continued to take relevant medicine for 22 d. 10 normal rats were selected as normal control group. General examination was conducted,and renal coefficient,serum contents of calcium,phosphorus,PTH,creatinine(Scr)and usea nitrogen(BUN)were detected after last medication as well as renal pathological change. RESULTS:Compared with normal control group,model group showed CRF sign,renal coefficient,the contents of phosphorus,PTH,Scr and BUN were increased,while the content of calcium was decreased(P<0.01);renal section showed obvious pathological characteristics. Compared with model group,CRF sign of rats were improved in lanthanum carbonate group,calcium carbonate group and lanthanum hydroxide groups. The renal coefficient(except for lanthanum hydroxide high-dose group),serum contents of phosphorus(except for calcium carbonate group),PTH(except for lanthanum hydroxide low-dose group and calcium carbonate group),Scr(except for lanthanum hydroxide low-dose group and calcium carbonate group)and BUN were all decreased,while serum content of calcium and calcium-phosphorucs product(only in calcium carbonate group)was increased(P<0.05 or P<0.01). There was no statistical significance in other difference. The renal section pathological characteristics were improved. CONCLUSIONS:Lanthanum hydroxide can improve renal function and reduce the level of serum phosphorus in CRF hyperphosphatemia model rats.
OBJECTIVE:To study the improvement effect of lanthanum hydroxide on chronic renal failure(CRF)hyperphosphatemia in rats. METHODS:CRF hyperphosphatemia rat model were induced and then randomly divided into model group,lanthanum carbonate group [0.3 g/(kg·d)],calcium carbonate group [4.2 g/(kg·d)] and lanthanum hydroxide high-dose,medium-dose and low-dose groups [1.5,1,0.5 g/(kg·d)] with 10 rats in each group. They were given adenine 0.2 g/(kg·d)intragastrically in the morning,and then given relevant medicine intragastrically in the afternoon;a week later,they stopped taking adenine but continued to take relevant medicine for 22 d. 10 normal rats were selected as normal control group. General examination was conducted,and renal coefficient,serum contents of calcium,phosphorus,PTH,creatinine(Scr)and usea nitrogen(BUN)were detected after last medication as well as renal pathological change. RESULTS:Compared with normal control group,model group showed CRF sign,renal coefficient,the contents of phosphorus,PTH,Scr and BUN were increased,while the content of calcium was decreased(P<0.01);renal section showed obvious pathological characteristics. Compared with model group,CRF sign of rats were improved in lanthanum carbonate group,calcium carbonate group and lanthanum hydroxide groups. The renal coefficient(except for lanthanum hydroxide high-dose group),serum contents of phosphorus(except for calcium carbonate group),PTH(except for lanthanum hydroxide low-dose group and calcium carbonate group),Scr(except for lanthanum hydroxide low-dose group and calcium carbonate group)and BUN were all decreased,while serum content of calcium and calcium-phosphorucs product(only in calcium carbonate group)was increased(P<0.05 or P<0.01). There was no statistical significance in other difference. The renal section pathological characteristics were improved. CONCLUSIONS:Lanthanum hydroxide can improve renal function and reduce the level of serum phosphorus in CRF hyperphosphatemia model rats.
引文
[1]Cernaro V,Santoro D,Lacquaniti A,et al.Phosphate bind ers for the treatment of chronic kidney disease:role of iron oxyhydroxide[J].Int J Nephrol Renovasc Dis,2016,2(9):11-18.
[2]Li JH,Yuan JM,Miao ZQ,et al.Effect of dietary nutrient density on small intestinal phosphate transport and bone mineralization of broilers during the growing period[J].PLo S One,2015,11(4):1-10.
[3]翟春娟.碳酸镧治疗慢性肾脏病高磷血症疗效和安全性的系统评价[D].济南:山东大学,2014.
[4]褚雷.慢性肾衰竭情况下胆汁酸代谢的临床及实验研究[D].济南:山东大学,2015.
[5]尹敬群,田君,晏南富,等.碳酸镧药物在高磷血症中的应用进展[J].生物化工,2016,2(3):54-57.
[6]刘永贵,于鹏,吴疆,等.新型磷结合剂的研究进展[J].现代药物与临床,2014(02):201-205.
[7]Yokozawa T,Zheng PD,Oura H,et al.Animal model of adenine-induced chronic renal failure in rats[J].Nephron,1986,44(3):230.
[8]储新年.腺嘌呤诱发大鼠慢性肾衰模型的病理学研究[D].延吉:延边大学,2007.
[9]卢志,魏芳,王立华,等.碳酸镧与碳酸钙对维持性血液透析患者FGF23的影响[J].中国医院药学杂志,2014,34(5):390-392.
[10]李杰,王芃,解砚英,等.聚苯乙烯磺酸镧对腺嘌呤致大鼠慢性肾衰高磷血症的治疗作用[J].中国临床药理学与治疗学,2007,12(5):530-534.
[11]楚非,邹万忠,孙锁柱,等.大鼠肾小管间质纤维化中肾小管上皮细胞表型转化的研究[J].中华肾脏病杂志,2003,32(1):10-14.
[12]Li WH,Zhang SJ.Risk factors of parathyroid dysfunction in elderly patients with chronic kidney disease undergoing hemodialysis[J].Adv Clin Exp Med,2015,24(6):1007-1012.
[13]陈俊蓉,陈利国,谢林林.关于腺嘌呤慢性肾衰实验模型的思考[J].实验动物科学,2013,30(2):65-67.
[14]蔡锋晴.慢性肾脏病患者血钙、磷和PTH水平与临床指标和肾脏病理的相关性研究[D].上海:复旦大学,2012.
[15]徐丰博,刘惠兰,孙懿.成纤维细胞生长因子23与血液透析患者血磷和甲状旁腺激素浓度的关系[J].首都医科大学学报,2013,34(3):450-453.
[2]Li JH,Yuan JM,Miao ZQ,et al.Effect of dietary nutrient density on small intestinal phosphate transport and bone mineralization of broilers during the growing period[J].PLo S One,2015,11(4):1-10.
[3]翟春娟.碳酸镧治疗慢性肾脏病高磷血症疗效和安全性的系统评价[D].济南:山东大学,2014.
[4]褚雷.慢性肾衰竭情况下胆汁酸代谢的临床及实验研究[D].济南:山东大学,2015.
[5]尹敬群,田君,晏南富,等.碳酸镧药物在高磷血症中的应用进展[J].生物化工,2016,2(3):54-57.
[6]刘永贵,于鹏,吴疆,等.新型磷结合剂的研究进展[J].现代药物与临床,2014(02):201-205.
[7]Yokozawa T,Zheng PD,Oura H,et al.Animal model of adenine-induced chronic renal failure in rats[J].Nephron,1986,44(3):230.
[8]储新年.腺嘌呤诱发大鼠慢性肾衰模型的病理学研究[D].延吉:延边大学,2007.
[9]卢志,魏芳,王立华,等.碳酸镧与碳酸钙对维持性血液透析患者FGF23的影响[J].中国医院药学杂志,2014,34(5):390-392.
[10]李杰,王芃,解砚英,等.聚苯乙烯磺酸镧对腺嘌呤致大鼠慢性肾衰高磷血症的治疗作用[J].中国临床药理学与治疗学,2007,12(5):530-534.
[11]楚非,邹万忠,孙锁柱,等.大鼠肾小管间质纤维化中肾小管上皮细胞表型转化的研究[J].中华肾脏病杂志,2003,32(1):10-14.
[12]Li WH,Zhang SJ.Risk factors of parathyroid dysfunction in elderly patients with chronic kidney disease undergoing hemodialysis[J].Adv Clin Exp Med,2015,24(6):1007-1012.
[13]陈俊蓉,陈利国,谢林林.关于腺嘌呤慢性肾衰实验模型的思考[J].实验动物科学,2013,30(2):65-67.
[14]蔡锋晴.慢性肾脏病患者血钙、磷和PTH水平与临床指标和肾脏病理的相关性研究[D].上海:复旦大学,2012.
[15]徐丰博,刘惠兰,孙懿.成纤维细胞生长因子23与血液透析患者血磷和甲状旁腺激素浓度的关系[J].首都医科大学学报,2013,34(3):450-453.