高镁对高磷诱导血管钙化的影响及其机制

目的 探讨高镁对高磷诱导血管钙化的影响及其可能的机制.方法 体外原代培养大鼠胸主动脉血管平滑肌细胞(VSMCs),用β甘油磷酸盐(β-GP)诱导钙化.VSMCs细胞被分为4组:对照组、高磷组(10 mmol/L β-GP)、镁干预组(10 mmol/L β-GP+3 mmol/LMgSO4)、镁通道抑制剂(2-APB)干预组(10 mmol/L β-GP+3 mmol/L MgSO4+10-4 mol/L 2-APB).采用茜素红染色及邻甲酚酞络合酮比色法检测细胞钙化情况;酶联免疫吸附法(ELISA)检测细胞碱性磷酸酶(ALP)活性;RT-PCR法和Western印迹法检测细胞核心结合因子α-1(Cbfα-1)的表达.24只雄性SD大鼠被随机分为3组:对照组(甲基纤维素灌胃+高磷饮食)、血管钙化组(硫酸腺嘌呤灌胃+高磷饮食)、高镁干预组(硫酸腺嘌呤灌胃+高磷高镁饮食).造模成功后测定大鼠主动脉脉搏波速率(PWV);采用yon Kossa染色及邻甲酚酞络合酮比色法检测胸主动脉钙化情况;免疫组织化学方法检测胸主动脉Cbfα-1表达.结果 细胞培养14 d后,与高磷组相比,镁干预组VSMCs钙盐沉积明显减少,ALP活性降低(P＜0.05),Cbfα-1表达下调;2-APB可抑制高镁对VSMCs的保护性作用.Cbfα-1的动态观察结果显示,镁干预组第3天Cbfα-1的表达下调(P＜0.05),其抑制效应随时间延长呈增强趋势.体内实验中,大鼠慢性肾衰竭血管钙化模型制备成功.和体外实验一致,与血管钙化组相比,高镁干预组大鼠血浆镁离子水平明显升高,胸主动脉PWV明显降低(P＜0.05),血管钙盐沉积程度亦明显减轻.免疫组织化学结果显示高镁可明显降低高磷诱导的Cbfα-1表达(P＜0.05).结论 高镁可抑制血管钙化,其机制可能与其抑制VSMCs骨源性分化相关.     

金属蛋白酶1组织抑制剂在慢性肾衰竭大鼠钙化动脉中的表达

目的 探讨金属蛋白酶1组织抑制剂（TIMP-1）是否参与慢性肾衰竭大鼠动脉钙化形成。 方法 雄性Wistar大鼠按随机数字表法分组,其中健康对照组8只,实验组36只。用2%腺嘌呤250 mg&#8226;kg－1&#8226;d－1灌胃制备动脉钙化模型。von Kossa染色观察主动脉、股动脉、肾动脉和冠状动脉钙化情况。RT-PCR和Western印迹检测主动脉TIMP-1表达。免疫组织化学方法检测TIMP-1、骨桥蛋白（OPN）、核心结合因子α1（Cbfα-1）在主动脉的表达。 结果 实验组大鼠给药2周后出现明显慢性肾衰竭表现,BUN、Scr、血磷、钙磷乘积和全段甲状旁腺素（iPTH）显著高于对照组（P < 0.01）;给药6周后主动脉、股动脉、肾动脉和冠状动脉中层出现不同程度的钙化。RT-PCR和Western印迹结果显示,实验组大鼠主动脉TIMP-1表达较对照组上调（P < 0.05）,随时间延长呈上升趋势。免疫组化的结果显示,给药后第2、4、6、8周主动脉平滑肌细胞TIMP-1蛋白表达均显著高于对照组（P < 0.05）;钙化主动脉出现Cbfα-1的阳性表达;OPN表达显著增多（P < 0.01)。TIMP-1的表达和OPN及Cbfα-1表达均呈正相关（r = 0.317,P = 0.000;r = 0.485,P = 0.000）。 结论 大鼠腺嘌呤肾衰竭模型血管钙化的病理变化与人类慢性肾衰竭血管钙化相似,是研究慢性肾衰竭血管钙化周期较短、较好的动物模型。TIMP-1高表达和慢性肾衰竭动脉血管钙化相关。     

腺嘌呤灌胃联合高磷饮食诱导慢性肾衰竭血管钙化大鼠模型的探讨

目的:观察腺嘌呤灌胃联合高磷饮食方法诱导的慢性肾衰竭血管钙化大鼠模型。方法:30只SD大鼠随机分为正常对照组及模型组,每组15只。实验第1~4周,模型组大鼠按250 mg/kg剂量给予腺嘌呤混悬液灌胃及含1.8%高磷饲料喂养,第5~6周腺嘌呤改为隔日灌胃。正常对照组灌胃等体积生理盐水。共给药6周。6周后杀检取材,苏木精-伊红(HE)染色法观察两组大鼠肾脏病理及主动脉钙化结节形成情况;检测主动脉血管壁钙含量及碱性磷酸酶(ALP)水平;全自动生化仪测定血钙(Ca2+)、血磷(P3-)、血肌酐(Scr)、血尿素氮(BUN)、血清全段甲状旁腺激素(i PTH)水平。结果:与正常对照组比较,模型组肾小球结构紊乱,肾小管扩张积水,腔内有炎性细胞的浸润,肾小管内棕褐色结晶沉积,肾脏间质纤维化,肾脏血管明显减少;模型组主动脉出现广泛的呈连续线性分布的钙化结节;模型组大鼠主动脉钙含量及ALP水平均明显升高,差异有统计学意义(P0.01);与正常对照组比较,模型组大鼠血P3-、Scr、BUN、i PTH水平均明显升高,差异有统计学意义(P0.01),血Ca2+水平明显下降,差异有统计学意义(P0.01)。结论:腺嘌呤灌胃联合高磷饮食是制备慢性肾衰竭血管钙化大鼠模型较为快速、可行、准确的方法,值得进一步推广。     

一步法5/6肾切除大鼠加高磷饮食快速建立肾衰竭致血管钙化动物模型法

目的：建立一种慢性肾衰竭快速诱导动脉血管钙化大鼠模型的实验方法,为进一步阐明肾衰竭所致血管钙化发病机制及其防治和新药的研究提供可靠的实验平台。方法：一步法5/6肾切除大鼠同时予以高磷饮食,28d后检测大鼠血清尿素氮、血肌酐、血钙、血磷和血甲状旁腺激素浓度;盐酸萃取法测定胸主动脉血管壁组织钙含量;von Kossa染色光镜下观察胸主动脉血管病理;pQCT仪测试胫骨近端骨密度。结果：大鼠血清尿素氮、血肌酐、血钙、血磷,血甲状旁腺激素和胫骨近端骨密度值,假手术组与正常组之间各项指标差异无统计学意义（P〉0.05）,手术组与假手术组之间各项指标差异有统计学意义（P〈0.05）。结论：本方法较传统方法相比,具有省时、省力、经济等特点,为慢性肾衰竭引起的心血管钙化研究提供了一个快速可靠的动物模型,为有效新药筛选提供可靠的动物模型。     

维持性血液透析患者主动脉钙化相关影响因素分析

目的：探讨维持性血液透析（MHD）患者主动脉钙化的相关影响因素。方法：采用胸部正位X线成像技术检测183例MHD患者主动脉钙化情况,将入选患者分为主动脉钙化组（A组）和主动脉无钙化组（B组）,透析前抽血检测血钙、血磷、全段甲状旁腺激素（iPTH）、C反应蛋白（CRP）和血清白蛋白（Alb）等指标,并计算钙磷乘积,比较两组年龄、透析龄和血清学指标的差异,将上述指标与主动脉钙化进行相关性分析,并对筛选出来的危险因素进行非条件Logistic回归分析。结果：A组和B组在年龄、透析龄、血磷、钙磷乘积和CRP水平方面,差异均有统计学意义（P〈0.01或P〈0.05）;MHD患者主动脉钙化的相关影响因素包括：年龄、透析龄、血磷、钙磷乘积及CRP;Logistic回归分析表明,年龄、透析龄和血磷是主动脉钙化的独立危险因素（P〈0.01）。结论：MHD患者主动脉钙化相当常见,主动脉钙化与年龄、透析龄、钙磷代谢和炎症状态有关。     

维持性血液透析患者血清SG K1水平与血管钙化的相关性研究

目的探讨维持性血液透析(maintenance hemodialysis,MHD)患者血清和糖皮质激素诱导激酶1(serum and glucocorticoid induced protenin kinase 1,SGK1)水平与血管钙化的相关性,为探究MHD患者血管钙化的发生机制提供理论依据。方法选取2019年1月至2019年12月山东第一医科大学附属青岛医院随访的MHD患者60例,采用胸部和腹部计算机断层扫描检测MHD患者血管钙化情况,根据胸主动脉、腹主动脉和冠状动脉存在的钙化或者斑块,分为血管钙化组和无血管钙化组,比较各组临床资料,包括性别、年龄、透析时间、体质量指数、既往基础疾病(高血压病等疾病)以及血磷、血钙、全段甲状旁腺素(intact parathyroid hormone,iPTH)、糖化血红蛋白、透析前后BUN、Scr和尿素氮下降率等实验室指标;采用酶联免疫吸附实验(ELISA法)测定MHD患者血清SGK1水平。结果与无血管钙化组患者相比,血管钙化组患者年龄、透析时间、高血压病、吸烟史、C反应蛋白、糖化血红蛋白、血磷、iPTH、钙磷乘积和碱性磷酸酶显著增高,差异均有统计学意义(P0.05)。血管钙化组患者血清SGK1浓度较无血管钙化对照组患者显著升高,差异有统计学意义(P0.05)。血清SGK1水平与血磷、iPTH以及钙磷乘积有相关性(P0.05)。Logistic回归分析结果显示,透析时间、血磷、iPTH、钙磷乘积和高水平SGK1为MHD患者发生血管钙化的独立危险因素(P0.05)。结论伴有血管钙化的MHD患者血清SGK1水平显著升高,且是MHD患者发生血管钙化的独立危险因素,SGK1可能在血管钙化发生中发挥重要的作用。     

鲑鱼降钙素联合骨化三醇治疗继发性甲状旁腺功能亢进观察

高磷血症、钙磷乘积升高和继发性甲状旁腺功能亢进（SHPT）可以导致血管钙化和增加心血管事件的风险,维持钙磷代谢平衡及全段甲状旁腺素（iPTH）水平已成为本领域的热点。本文采用鲑鱼降钙素联合活性维生素D治疗尿毒症患者SHPT取得了一定疗效,现报道如下。     

慢性肾脏疾病患者钙磷代谢的控制对血管钙化的影响

目的观察慢性肾脏疾病（chronickidneydisease,CKD）3期开始纠正钙磷代谢紊乱对患者血管钙化的影响。方法选择本院门诊或住院的CKD3～4期非透析患者80例,按随机数字表法分为干预组及观察组,每组40例。干预组进行钙磷代谢紊乱严格干预,观察组则给予CKD的常规治疗,观察并比较2组患者的血压、血尿素氮、血肌酐、血钙、血磷、全段甲状旁腺素（intactparathyroidhor—mone,iPTH）、血红蛋白（hemoglobin,Hb）、血白蛋白等指标,同时通过腹部、骨盆、手部x线平片进行血管钙化的定量测量。结果2组治疗后的血钙、血磷、钙磷乘积、iPTH、收缩压（systolicbloodpressure,SBP）和血白蛋白较治疗前明显变化,而舒张压（diastolicbloodpressure,DBP）和Hb较治疗前无明显变化（P〉O．05）。干预组血钙治疗后高于治疗前（P〈O．05）,亦高于对照组（P〈O．05）;干预组和观察组血磷和血白蛋白治疗前相比均升高,但观察组升高更显著（P〈0．05）。干预组和观察组血SBP和iFrrH与治疗前相比均降低,但干预组降低更显著（P〈O．05）。干预组发生血管钙化4例,观察组发生血管钙化10例,干预组血管钙化的发生率低于观察组（P〈O．05）。结论钙磷代谢紊乱参与了CKD血管钙化的进展,在CKD3期开始干预可明显延缓其进展,提高患者预后质量。     

甲状旁腺切除术后维持性血液透析患者腹主动脉钙化的改变

目的 观察维持性血液透析(maintenance hemodialysis,MHD)合并继发性甲状旁腺功能亢进(secondary hyperparathyroidism,SHPT)患者行甲状旁腺切除术(parathyroidectomy,PTX)后腹主动脉钙化及生化指标的发展变化.方法 回顾性分析完成2年随访的严重SHPT患者,按是否行PTX分成PTX手术组和非手术组,观察术后2年腹主动脉钙化评分(abdominal aortic calcification score,AACS)、血清全段甲状旁腺素(iPTH)、血钙、血磷等变化.PTX手术组按照术后2年腹主动脉钙化有无进展分为进展组和非进展组,对比两组的年龄、透析龄、iPTH、血钙、血磷、钙磷乘积等指标,分析腹主动脉钙化进展的相关因素.结果 共纳入44例MHD合并SHPT患者,PTX手术组26例,非手术组18例.PTX手术组与非手术组基线资料比较,透析龄差异有统计学意义(P<0.05),而性别、年龄、高血压史等差异均无统计学意义.与术前比较,PTX手术组患者术后2年血iPTH、血钙、血磷均降低(均P<0.05),AACS前后差异无统计学意义.患者术后2年有8例(30.77%)腹主动脉钙化加速进展,8例(30.77%)腹主动脉钙化好转,10例(38.46%)腹主动脉钙化稳定.患者术后2年腹主动脉钙化非进展组iPTH值低于进展组[(20.62+6.44) ng/L比(132.72±76.83) ng/L,P<0.05],而非进展组术前AACS高于进展组[(13.11±2.71)分比(2.00±1.41)分,P<0.05].非手术组患者2年后AACS高于基线水平[(10.44±1.65)分比(8.05±1.26)分,P<0.05],血磷及钙磷乘积显著下降(均P<0.05),iPTH、血钙等水平无明显变化(均P>0.05).Pearson相关分析结果显示,PTX手术组术后2年AACS相对于术前的下降值与iPTH下降值(r=0.534,P=0.012)、血钙下降值(r=0.643,P=0.004)、血磷下降值(r=0.897,P<0.001)、钙磷乘积的下降值(r=0.568,P=0.021)呈正相关,与术前AACS值呈负相关(r=-0.647,P=0.014).结论 小样本资料显示,相比非手术治疗,PTX可长期纠正甲状旁腺素、钙、磷代谢紊乱,并有阻止腹主动脉钙化进展甚至逆转血管钙化的可能,而腹主动脉钙化逆转可能与iPTH、血Ca、血P、钙磷乘积的下降程度相关.     

维持性血液透析患者血管钙化的发生情况及相关危险因素分析

目的探讨维持性血液透析患者的血管钙化发生情况及相关危险因素分析。方法选择血液透析患者91例,记录相关人口学资料及临床资料,完善实验室检查。分别以X光片（腰椎侧位、双手、骨盆）评价血管钙化情况。结果91例患者中无血管钙化者22例,有不同程度血管钙化者69例;轻度钙化38例（占41．76％）,中度钙化14例（占19．72％）,重度钙化17例（占23．94％）;统计学分析显示2组间年龄、血磷和钙磷乘积有统计学差异（P〈0．05）;单因素分析显示年龄、血磷、钙磷乘积和未服用活性维生素D是血管钙化的危险因素,多因素分析显示年龄、血磷、未服用活性维生素D为血管钙化独立影响因素。结论血管钙化是维持性血液透析患者常见并发症,且发病率较高,高龄、高磷血症、高钙磷乘积及合理使用活性维生素D在钙化发生、发展中有重要作用。     

Sodium thiosulfate attenuates high phosphorous induced vascular calcification in rats with 5/6 nephrectomy

Objective To observe the expression of Klotho and Na+/Pi cotransporter in high phosphorous-induced rats with 5/6 nephrectomy and its relationship with vascular calcification, as well as to investigate the effect of early intervention by sodium thiosulfate (STS) on the progression of vascular calcification. Methods Either 5/6 nephrectomy (n=21) or sham operation (n=14) was conducted on 35 Sprague Dawley rats, who were then fed with high phosphorus (HP) diet or normal phosphorus (NP) diet for 16 weeks respectively. The rats were divided into 5 groups as follows: (1) remnant kidney rats receiving HP diet (NHP, n=7), (2) remnant kidney rats receiving NP diet (NNP, n=7), (3) sham operation rats receiving NP diet (SNP, n=7), (4) sham operation rats receiving HP diet (SHP, n=7), (5) remnant kidney rats receiving HP diet with STS (THP, n=7). The treatment group was given STS intraperitoneally three times a week for 16 weeks. At the end of the 16th week, rats tail artery blood pressures were tested, serum creatinine (Scr), calcium (Ca2+), phosphorus (P3+), FGF23, iPTH and urine protein were examined. Throacic aorta and kidney were then removed. Vascular calcification was confirmed by Von kossa staining. Klotho and Pit-1 expression in aortas were determined by immunohistochemistry. Renal lesion was determined by PASM-Masson staining. Renal Klotho and NaPi-2a mRNA were determined by real time RT-PCR. Results After 16 weeks, Scr, P3+, FGF23, iPTH, uric protein and blood pressure were significantly higher in NHP than those in SNP rats (all P＜0.05). PASM-Masson staining revealed typical renal pathology of chronic renal failure in NHP group. With the treatment of STS, THP rats showed significant decrease in Scr, P3+, FGF23, iPTH, uric protein and blood pressure by comparison with NHP group (all P＜0.05). Significant vascular calcification was found in NHP group while NNP and SHP group occasionally had vascular calcification; THP group had marked alleviation of vascular calcification. The aorta and renal expression of Klotho decreased remarkably while expression of Pit-1 and NaPi-2a increased significantly in NHP compared with SNP group (all P＜0.05). Accordingly, the aorta and renal expression of Klotho increased and Pit-1 and NaPi-2a decreased significantly in THP compared with NHP group (P＜0.05). Conclusions The early intervention of sodium thiosulfate might regulate Klotho and Na+/Pi cotransporter expression in both aorth and kidney, decreasing serum phosphate, delaying progression of vascular calcification and improving renal function.     

Effects of Phosphonoformic Acid and Renagel on Renal Type IIa Sodium-Dependent Phosphate Cotransporter mRNA Expression in Hyperphosphatemia Rats

Objective: To investigate the effects of phosphonoformic acid (PFA) and sevelamer hydrochloride (Renagel) on renal type IIa sodium-dependent phosphate cotransporter (NaPi-2) mRNA expression in hyperphosphatemia rats. Methods: Thirty rats were randomly divided into five groups based on the diet for 2 weeks after 5/6 nephrectomy (Nx): Nx + high-phosphate (HP; 1.2% P) diet; Nx + low-phosphate (LP; 0.2% P) diet; HP + PFA (injected with 0.15 g/kg PFA daily); HP + Saline (injected with the same amount of saline daily); and HP + Renagel (2%) group. Another 12 rats were sham operated and divided into Sham + HP and Sham + LP groups. Serum ionized calcium, phosphorus (P), and intact parathyroid hormone (iPTH) were measured on days 2, 7, and 14. Serum 1,25(OH)₂D₃ was measured on day 14 and NaPi-2 mRNA levels were assayed by RT-PCR. Results: PFA decreased iPTH level but had no effect on NaPi-2 mRNA expression. Renagel decreased serum P and iPTH levels, but upregulated renal NaPi-2 mRNA expression. Conclusions: Both PFA and Renagel are effective drugs to decrease iPTH level and they might be potential candidates for treatment of clinical secondary hyperparathyroidism. Renagel can also decrease serum P and upregulate renal NaPi-2 mRNA expression.     

维持性血液透析患者甲状旁腺激素水平的临床分析

目的 探讨慢性肾功能衰竭维持性血液透析患者不同血浆全段甲状旁腺激素水平影响因素的差异.方法 在2006年9月至2009年8月期间于我院门诊维持性血液透析慢性肾功能衰竭患者中随机选择血浆全段甲状旁腺激素>1000 μg/L患者20例(高甲状旁腺激素组);血浆全段甲状旁腺激素<150 μg/L的患者20例(低甲状旁腺激素组).对两组患者的临床资料进行回顾性分析.结果 两组患者年龄、病死率、原发病、血肌酐、尿素氮、血浆白蛋白、血磷及钙磷乘积方面比较差异有统计学意义(P < 0.05);两组患者性别、血红蛋白、胆固醇、甘油三酯、血钙及二氧化碳结合力方面比较差异无统计学意义(P > 0.05).结论 在慢性肾功能衰竭维持性血液透析中高龄及糖尿病肾病患者低甲状旁腺激素水平的发生率明显增高;低甲状旁腺激素水平的患者病死率明显增高;高甲状旁腺激素水平患者的血肌酐、血磷及钙磷乘积水平明显高于低甲状旁腺激素水平患者,营养状况也优于后者.     

Role of type Ⅲ sodium-dependent phosphate cotransporter PiT-1 in cardiac damages in uremic rats fed with high phosphate diet

Objective To evaluate the expression of type III sodium-dependent phosphate cotransporter (Pit-1) in cardiac damages in uremic rats fed with high phosphate diet. Methods Male SD rats were given an adenine and high phosphate diet as uremic rats (n＝18, uremic rats) or just high phosphate diet (NHP group, n＝6). After making uremic models, 18 rats were randomly divided into three groups as follow: uremic rats received high phosphate diet only (UHP group, n＝6); uremic rats received high phosphate diet and intraperitoneal phosphonoformic acid (PFA) 0.15 g·kg-1·d-1 (UHP＋PFA group, n＝6 ); uremic rats received high phosphates diet and intraperitoneal normal saline 0.15 g·kg-1·d-1 (UHP＋NS group, n＝6). At the end of 4th week and 8th week, serum Scr, Ca, P, and urine Ca, P were examined. At the end of the 8th week, the rats were sacrificed, and left ventricle weight, myocyte diameter, cardiac fibrosis were measured. The expression of PiT-1, TGF-β1, Cbfα-1, phosphorylation p38 mitogen-activated protein kinase (p-p38MAPK) and ERK (p-ERK) were determined by Western blotting. Results At the end of 4th week, Scr was higher in the uremic rats than that in the NHP rats. There was no significant difference of serum Ca, P, 24 h urinary P and Ca clearance among 4 groups (P＞0.05). At the end of 8th week, serum P was higher and Ca was lower in uremic groups than that in NHP group (P＜0.05). There was no significant difference of Scr, serum Ca, P, 24 h urinary P and Ca clearance among uremic groups (P＞0.05). Compared with those in NHP rats, the left ventricle weight, myocyte diameter, and the collagen volume fraction (%) increased in UHP group and UHP＋NS group (all P＜0.05), however, these parameters were ameliorated in UHP＋PFA group significantly (all P＜0.05). Western blotting showed that the expressions of PiT-1, TGF-β1, Cbfα-1, p-p38MAPK and p-ERK were higher in UHP group and UHP＋NS group than that in NHP group and they decreased significantly in UHP＋PFA group (all P＜0.05). Conclusions There are significant cardiac damages in uremic rats received high phosphate diet, companied with increased PiT-1, TGF-β1, Cbfα-1, p-p38MAPK, p-ERK expressions. The adverse effects are ameliorated by PiT-1 blocker, indicating that PiT-1 play a role in high phosphate diet induced cardiac damages in uremic rats.     

Hypercalcemia fails to suppress elevated serum parathyroid hormone concentrations during lactation in rats

We have previously reported that increased serum immunoreactive parathyroid hormone (iPTH) in the lactating (L) rat is generally accompanied by hypocalcemia when diets containing 0.4% calcium (Ca) or less are fed. However, instances were also observed in which elevated iPTH levels did not coincide with a hypocalcemic signal. To test the hypothesis that iPTH levels can remain elevated even in the presence of hypercalcemia in lactation, a diet containing 1.2% Ca and 0.4% phosphorus (P) was fed to lactating rats in three experiments (A, B, and C) to achieve serum ionized calcium (ICa) levels approximately 10% above levels for nonmated (NM) controls. The serum ICa of NM controls fed the 1.2% Ca diet was slightly, but significantly, elevated, and serum iPTH (determined by an N-terminal specific assay) was significantly suppressed compared with NM controls fed a 0.4% Ca diet. In experiment A, L rats fed a 1.2% Ca diet had 81% higher serum iPTH levels than NM controls fed the same diet in spite of a mean (+/- SEM) ICa level of 1.77 +/- 0.05 mM for L rats versus 1.46 +/- 0.01 mM for NM controls; NM controls fed a 0.4% Ca diet had serum ICa of 1.37 +/- 0.01 mM. This novel finding of significantly higher iPTH and ICa in L compared with NM rats fed a 1.2% Ca and 0.4% P diet was confirmed in experiment B with eight rats in each group of L or NM rats fed either the 1.2% or the 0.4% Ca diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal alterations in experimental diabetes: Role of a primary disturbance in calcium homeostasis

Summary Chronic diabetes mellitus in the rat is attended by a reduced bone turnover and growth arrest, decreased circulating immunoreactive parathyroid hormone (iPTH), and hypercorticosteronism. Since chronic insulin deficiency in the rat is associated with intestinal hyperabsorption of calcium and a positive calcium balance that may account for the decreased iPTH, as well as other hormonal alterations observed in these animals, we studied the effect of long-term (5 week) dietary calcium restriction (0.1% Ca, 0.8% P) in control and streptozotocin-induced diabetic rats. Chronic diabetic rats reared on a normal calcium (1.2% Ca) diet had increased serum calcium and phosphate (Pi) concentrations and were markedly hypercalciuric and phosphaturic compared with controls. Serum corticosterone was increased and iPTH markedly decreased in the diabetic animals. Dietary Ca restriction (0.1% Ca) decreased urinary calcium excretion and resulted in a comparable phosphaturic response in both control and diabetic rats. Moreover, although Ca restriction in diabetic animals had no appreciable effect on serum insulin, serum glucose, or urinary glucose excretion, it was associated with a marked increase in circulating iPTH; this resulted in serum concentrations comparable with that observed in control animals reared on the low Ca diet. These results support the hypothesis that the decreased circulating iPTH observed in chronic diabetic rats results predominantly from their intestinal hyperabsorption of Ca. In contrast to control animals, diabetic rats reared on a low Ca diet failed to maintain their serum Ca despite the marked increase in serum iPTH and striking decrease in calciuria, thus underscoring the reliance of these animals on intestinal hyperabsorption of Ca to maintain Ca balance under conditions of adequate Ca intake. Serum corticosterone was insignificantly altered by dietary Ca restriction in control rats; hypercorticosteronism, characteristically observed in diabetic rats, was normalized by Ca restriction. We conclude that a primary disturbance in Ca homeostasis may contribute, in part, to hormonal alterations observed in chronic experimental diabetes.     

高通量血液透析联合血液灌流对维持性血液透析患者血清钙、磷及甲状旁腺激素代谢的影响

目的 研究高通量血液透析(HFD)联合血液灌流(ⅢP)对维持性血液透析患者血清钙磷及甲状旁腺激素代谢的影响.方法 40例维持性血液透析患者随机分为对照组(高通量血液透析)和观察组(高通量血液透析联合血液灌流),在试验前及试验1和3个月后分别检测两组患者透析前肌酐(Cr)、尿素氮(BUN)、磷(P)、钙(Ca)、全段甲状旁腺激素(iPTH)等生化指标并进行比较.结果 高通量血液透析联合血液灌流与单纯高通量透析者间比较,血清BUN、Cr、Ca差异无统计学意义(P＞0.05);但iPTH、P在两种血液净化模式下差异有统计学意义(P＜0.05).结论 HFD+ HP血液净化方式能有效降低维持性血液透析患者P、iPTH水平,进而可能会提高其生存质量.     

左归丸对5/6肾大部切除模型并肾性骨病大鼠骨代谢指标的影响

目的:探讨左归丸对5/6肾大部切除模型并肾性骨病大鼠骨代谢的影响。方法:SPF级Wistar大鼠进行5/6肾大部切除并给予高磷饮食诱导肾性骨病模型。造模大鼠分为模型组、左归丸组、骨化三醇组,并设假手术组。左归丸与骨化三醇治疗4周、12周时,检测血肌酐(Scr)、尿素氮(BUN)、血清碱性磷酸酶(ALP)、血清全段甲状旁腺激素(iPTH)、血钙(Ca2+)、血磷(P3-);药物干预12周麻醉处死大鼠,双能X线测量大鼠股骨骨密度(BMD)。结果:12周时,模型组大鼠出现了Scr、BUN、ALP、iPTH、磷升高,血Ca2+下降。左归丸能明显降低Scr、BUN水平,与模型组比较差异有统计学意义(P<0.01,P<0.05);与骨化三醇组比较差异有统计学意义(P<0.01,P<0.05)。左归丸组大鼠ALP、iPTH、血磷水平与模型组比较明显下降(P<0.05),血钙水平明显升高(P<0.01),左归丸组大鼠骨密度与模型组比较明显改善(P<0.01)。结论:左归丸通过调节钙磷代谢及参与成骨细胞代谢,对iPTH有直接的抑制作用,能改善肾性骨病的骨营养不良。     

糖尿病肾病患者血清BMP2、BMP7水平与钙磷代谢的关系

目的探讨糖尿病肾病患者血清骨形态蛋白-2(BMP2)、骨形态蛋白-7(BMP7)水平与钙磷代谢的关系。方法选取2016年11月至2018年11月西电集团医院收治的126例糖尿病肾病患者作为研究组,采用系统性回顾性分析法分析研究组临床资料,根据不同分期阶段慢性肾脏病(CKD)将患者分为5组,分别为CKD 1组22例、CKD 2组21例、CKD 3组27例、CKD 4组31例、CKD 5组25例,另选取36例同期于西电集团医院门诊体检的健康人群作为对照组,测定患者血清BMP2、BMP7、血磷、血钙、肌酐(Scr)、甲状旁腺激素(iPTH),分析血清BMP2、BMP7与钙磷代谢的关系。结果①对照组与CKD 1~2期在血磷、血钙、Scr、iPTH、BMP2、BMP7水平之间差异无明显统计学意义(P>0.05);与对照组比较,CKD 4期以后血钙及血清BMP7水平明显降低(P<0.05);CKD 3期以后血清Scr、iPTH、BMP2水平明显开始升高、血清BMP7水平明显开始降低(P<0.05);CKD 4期以后血磷、Scr、iPTH、BMP2水平明显升高,血钙、BMP7水平明显降低;CKD 5期的变化情况同CKD 4期;②经Pearson积差相关分析,血清BMP2与血磷、Scr及iPTH呈正相关,与血钙呈负相关(P<0.05);BMP7与血钙呈正相关,与血磷、Scr及iPTH呈负相关(P<0.05);③经多因素多元逐步回归分析,血磷、血钙、Scr及iPTH均为影响糖尿病肾病患者血清BMP2、BMP7水平的相关因素(P<0.05)。结论CKD 3期以后血清BMP2开始升高、BMP7开始降低,且血清BMP2与血钙呈明显负相关,BMP7与血磷、Scr及iPTH呈明显负相关;钙磷代谢情况可能是糖尿病肾病患者血清BMP2升高、BMP7降低的重要相关因素。