快胃片对慢性肾衰竭合并高磷血症大鼠钙磷代谢及胃肠道相关指标的影响

Effect of Kuaiweipian on Calcium and Phosphorus Metabolism and Gastrointestinal Related Indicators in Rats with Chronic Renal Failure and Hyperphosphatemia

目的:观察快胃片对慢性肾衰竭合并高磷血症大鼠钙磷代谢及胃肠道相关指标的影响。方法:6周龄SD雄性大鼠取10只行假手术并正常饲料喂养,作为正常对照组(sham组)。另取46只大鼠,采用5/6肾切除法联合高磷饮食(磷含量1.03%)喂养4周建立慢性肾衰竭合并高磷血症的大鼠模型。造模成功后随机均分为模型对照组(模型组)、尿毒清颗粒+碳酸钙D3咀嚼片组(碳酸钙组)、尿毒清颗粒+快胃片低剂量组(低剂量组)、尿毒清颗粒+快胃片高剂量组(高剂量组)。成模2 d后开始给予相应药物,给药4周后检测大鼠钙(Ca^(2+))、磷(P^(3-))、碱性磷酸酶(ALP)、甲状旁腺激素(PTH)、血肌酐(Scr)、尿素氮(BUN)、血尿酸(UA)、24 h尿蛋白定量(24 h UP)、胃促生长素(Ghrelin)、生长抑素(somatostatin,SS)及肠道分泌型免疫球蛋白A(secretory immunoglobulin A,SIg A)的变化,并在给药结束后,取右侧肾脏,观察肾小球、肾小管及肾间质的改变。结果:给药前,观测指标于各造模组间差异无统计学意义,而各造模组与sham组间差异有统计学意义(P<0.05)。给药4周后,模型组大鼠与给药前相比,P^(3-)、ALP、PTH、Scr、BUN、UA及24 h UP显著增长(P<0.01),Ca^(2+)有所下降(P<0.05);与模型组相比,3个治疗组大鼠P^(3-)、ALP、PTH、Scr、BUN、UA及24 h UP明显下降(P<0.01),Ca^(2+)明显上升(P<0.01)。对胃肠道指标的检测显示,给药4周后,与自身给药前相比,sham组和模型组Ghrelin水平有所增加(P<0.05),碳酸钙组、低剂量组无明显变化(P>0.05),高剂量组较前有所减少(P<0.05),而所有组别大鼠SS水平均明显下降(P<0.01),SIgA水平明显升高(P<0.01),各组大鼠SS下降幅度为sham组<高剂量组<碳酸钙组≈低剂量组<模型组,IgA增长幅度为模型组≈碳酸钙组<sham组≈低剂量组<高剂量组。模型组肾脏在HE、Masson染色下观察显示肾组织结构紊乱,肾小球囊内和肾小管见大量蓝染物质沉积,PAS染色中阳性率高,透射电镜下足细胞趋于坏死,细胞器肿胀;3个治疗组大鼠与模型组相比均较轻微,各治疗组疗效相近。结论:快胃片或碳酸钙D3咀嚼片联合尿毒清颗粒均可降低CRF大鼠P^(3-),且对肾功能具有一定保护作用,疗效相近。快胃片联合尿毒清颗粒对胃肠道分泌具有一定改善作用。

Objective:In intervention of rats in CKD-G5D by Kuaiweipian,observe the influence of calcium and phosphorus metabolism and gastrointestinal related indicators in rats.Methods:6-weeks male rats were taken five-sixths nephrectomy and given high-phosphorus(phosphorus:1.03%)fodder to complete the models.And they were randomly divided into model group,Niaoduqing Grains+Calcium Carbonate D3(Ca group),Niaoduqing Grains+low-dose Kuaiwei Tables(low-dose group)and Niaoduqing Grains+high-dose Kuaiwei Tables(high-dose group).Another 10 rats were given sham operation and fed with normal diet as sham group.Observe the levels of Ca^(2+),P^(3-),ALP,PTH,Scr,BUN,UA,Ghrelin,Somatostatin(SS),Secretory Immunoglobulin A(SIg A),24-hour urinary protein(24 h UP)before and after the treatment.After the treatment,the right kidney of rat was taken to observe the change of glomerulus,renal tubules and renal interstitium.Results:Before treatment,the observation indexes of each model groups were statistically different from those of the sham group(P<0.05)and there was no significant difference among the model groups(P>0.05).After 4-week treatment,the level of P^(3-),ALP,PTH,Scr,BUN,UA and 24 h UP in model group were increased(P<0.01)and Ca^(2+)was down(P<0.05)compared with those before treatment.The level of P^(3-),ALP,PTH,Scr,BUN,UA and 24 h UP in the treatment groups was significantly lower than those of the model group(P<0.01),and Ca was higher(P<0.01).In terms of gastrointestinal indicators,after 4-weeks treatment,compared with before treatment,the level of Ghrelin was increased in sham group and model group(P<0.05),decreased in high-dose group(P<0.01),and no change in Ca^(2+)group and low-dose group(P>0.05).However,the level of SS in all groups was decreased(P<0.01)and the level of sIgA was increased(P<0.01).The decline range of SS in all group was control group<high-dose group<Ca^(2+)group≈low-dose group<model group.And the rising rage of sIgA in each model group was model group≈Ca^(2+)group<control group≈low-dose group<high-dose group.In terms of pathologic examination,there were disorder of organizational structure,high positive rate of PAS staining,high fibrosis and large number of necrotic podocytes tended to be and swelled organelles in model group.The pathologic examination in three treatment groups were slightly lower than those in the model group,and the therapeutic effect of each treatment group was similar.Conclusion:Kuaiweipian or medicinal charcoal combined with Niaoduqing Grains,whether high dose or low dose,could decrease the level of P^(3-)and protect renal function,and there was no difference between them.Kuaiweipian combined with Niaoduqing Grains could regulate the secretion of gastrointestinal hormone.