改良UW灌注液治疗新生猪急性肾小管坏死的实验研究

Objective To determine the effect of the modified UW (University of Wisconsin)solution in the treatment of acute renal tubular necrosis in newborn swine. Methods Ten one-week-old newborn swine were used to establish the animal model of acute renal tubular necrosis by clamping their renal arteries,and were divided into two groups: the model group( n = 5 ) and the treatment group ( n = 5 ) in which fructose diphosphate sodium UW solution was used. Sham surgery was performed on other five swine, which were used as the sham group. At 12 h,l d,2 d,3 d and 7 d after the operation,the urine volume,urine protein,blood urea nitrogen(BUN) and creatinine(Cr) were determined. At 12 h ,24 h and 7 d after the operation ,renal pathological examination was conducted. Results The renal pathological examination and the blood biochemistry tests showed that the animal model was successful. BUN and Cr in the model group and the treatment group were significantly higher than those in the sham group at 12 h after operation(P ＜0. 05) ,and they arrived at their peak values at 2 d after operation,showed remarkable decline at 7 d,especially in treatment group,and returned to the level of the sham group. The urine protein in the model group and treatment group were higher than those in the sham group at various times(P ＜0.05 or P ＜0.01) and it peaked at 1 d after operation,then declining gradually,especially in the treatment group. Compared with the sham group,there were a significant decrease in the urine volume at various times in the model group(P ＜0. 05 or P ＜0. 01 ) ,while in the treatment group,the decrease in the urine volume were significant only at 12 h, 1 d and 2 d( P ＜ 0. 05 ) ,and turned insignificant at 3 d and 7 d. The pathological examination showed that the pathological changes in the treatment group were significantly milder than those in the model group. Conclusion The modified UW solution is effective in reducing the acute renal tubular necrosis in newborn swine.     

角质细胞生长因子-1在脓毒症大鼠肾脏的表达及意义

目的 探讨角质细胞生长因子-1(keratinocyte growth factor-1,KGF-1)在脓毒症大鼠肾脏的表达及意义.方法 将80只6周龄健康雄性Wistar大鼠随机分成手术组和假手术组(各40只).用盲肠结扎穿刺法制备脓毒症大鼠模型.两组分别在术后3h、6h、12h、24h和36h留取血液及肾脏标本,HE染色光镜观察大鼠肾脏病理学变化,测定血肌酐(Cr)、尿素氮(BUN)浓度及WBC计数,免疫组织化学SABC染色法检测KGF-1蛋白表达,实时荧光定量PCR法检测KGF-1mRNA的基因相对表达量.结果 与假手术组相比,手术组24h肾损伤最严重,可见肾小管空泡变性,大量中性粒细胞、淋巴细胞及单核细胞浸润、局部有点状出血、坏死;血Cr、BUN术后3h无明显升高,6h后升高,24h达峰值,36h略有下降,差异有统计学意义(P<0.01).KGF-1蛋白及基因表达6h最强,12h有所下降,24h出现第二次表达高峰,36h又有所下降,均明显高于假手术组(P<0.01).KGF-1mRNA与BUN成正相关(r=0.504,P<0.01),与Cr成正相关(r=0.382,P<0.05).结论 KGF-1在正常大鼠肾脏中即有表达,主要集中在髓质肾小管上皮细胞,皮质肾小管也有分布.脓毒症受损肾脏的KGF-1表达显著增强且与肾脏损伤程度呈正相关,推测KGF-1是影响感染后肾脏损伤修复的重要因素之一.

Abstract：

Objective To investigate the expression and significance of keratinocyte growth factor-1(KGF-1) in the kidneys of septic rats.Methods Eighty male Wistar rats were randomly divided into the sepsis group and sham operation group.Either group was divided into 3-hour,6-hour,12-hour,24-hour and 36-hour subgroups,with 8 rats in each.Sepsis models were established by cecum ligation perforation (CLP).The kidney and blood samples were respectively taken for pathological study.Serum creatinine (Cr) and blood urea nitrogen (BUN) level determination and leukocyte counting were performed.KGF-1 protein was detected by immunohistochemical method and the expression of KGF-1 genes by real time PCR.Results The renal tubules in sepsis group were injured most at 24h after operation,which were infiltrated by considerable neutrophilic granulocytes,leukomonocytes and mononuclear cells,with vacuolar degeneration,focal hemorrhage and necrosis under the light microscopy.Serum Cr and BUN increased from 6h after operation,and reached the peak at 24h after operation in sepsis group,which were significantly different in those of sham operation group (P< 0.01).Compared with sham operation group,the expression of KGF-1 protein and genes of sepsis group increased significantly and reached the peak at 6h after operation.KGF-1mRNA was positively correlated with BUN and Cr (r=0.504,P<0.01;r=0.382,P<0.05).Conclusion KGF-1 was also expressed in normal kidneys,mainly in tubule epithelial cells of renal medulla and also in that of renal cortex.The expression of KGF-1 in sepsis group was obviously higher than that of sham operation group,and was positively correlated with the degree of kidney damage after infection.KGF-1 was speculated to be one of the protective factors affecting the repair of impaired kidneys caused by infection.     

电针可下调缺氧缺血性脑损伤幼鼠大脑皮层硫化氢含量

Objective To establish hypoxic-ischemic brain damaged (HIBD) rat model,investigate whether H2S and cystathionine-β-synthase (CBS), the key enzyme for its generation, may be a mediator of electro-acupuncture(EA) stimulation treatment for HIBD. Methods Thirty-two healthy Sprague-Dawley neonatal rats were divided into four groups randomly: sham control group ( n = 8 ); sham + EA group ( n =8); HIBD control group ( n = 8); and HIBD + EA group ( n = 8 ). HIBD rat models were established on their 7-day-old. From the next day ,rats of sham + EA group and HIBD + EA group were electric stimulated 30 min daily for 14 d,BAIHUI and DAZHUI as the acupoints. Control ones were just fixed at the same time,without acupuncture. The rats were sacrificed on the 22 nd day, one day after the treatment course. Cortical H2S concentration was measured by sensitive sulphur electrode assay. The CBS protein expression was measured by western blot analysis and immunohistochemistry for localization. Results The concentration of cortical H2S in HIBD control group was (26. 83 ± 4. 31 ) nmol/mg protein, which was significantly higher than that of sham control group[(22. 78 ± 1.54) nmol/mg protein]( P ＜ 0. 01 ). The H2 S levels in HIBD + EA group and sham + EA group were ( 18.08 ± 2.71 ) nmol/mg protein and ( 18.91 ± 2. 78 ) nmol/mg protein, respectively. Compared with corresponding control group, they were much lower( P ＜ 0. 01 ). The expression of CBS protein in rats with EA stimulation decreased in cortex compared to corresponding control group( P ＜0. 05 ).Conclusion EA can down-resulate H2S/CBS pathway. This may be one of the mechanisms of how EA contributes to the recovery of brain damage.     

间断静脉滴注3%高渗盐水与20%甘露醇治疗小儿急性脑水肿的疗效对比

Objective To compare the clinical efficacy of 3% hypertonic saline with 20% mannitol in the treatment of acute brain edema in children.Methods Twenty children with acute brain edema were randomly divided into hypertonic saline(HS) group and mannitol group.HS group and mannitol group were given 3% HS solution or 20% mannitol respectively.Main outcome measurements included intracranial pressure(ICP),mean arterial pressure(MAP),central venous pressure(CVP),cerebral perfusion pressure (CPP),serum electrolytes,plasma osmolality,renal function and urine volume.Results Both 3% HS and 20% mannitol were effective in reducing ICP(P ＜0.05).Therapeutic effect lasted(4.5±1.2) h in HS group and(3.2±1.5) h in mannitoi group.3% HS had a longer duration of action than marmitol(P＜0.05).At the time point of 2 hours after treatment,MAP and CPP of HS group increased more than those of mannitol group(P＜0.05).Conclusion Both 3% HS and 20% mannitol could rapidly decrease ICP.3% HS has a longer duration of action in reducing ICP than 20% mannitol.3% HS is more effective in stabilizing circulation and improving CPP than 20% mannitol.     

间断静脉滴注3%高渗盐水与20%甘露醇治疗小儿急性脑水肿的疗效对比

Objective To compare the clinical efficacy of 3% hypertonic saline with 20% mannitol in the treatment of acute brain edema in children.Methods Twenty children with acute brain edema were randomly divided into hypertonic saline(HS) group and mannitol group.HS group and mannitol group were given 3% HS solution or 20% mannitol respectively.Main outcome measurements included intracranial pressure(ICP),mean arterial pressure(MAP),central venous pressure(CVP),cerebral perfusion pressure (CPP),serum electrolytes,plasma osmolality,renal function and urine volume.Results Both 3% HS and 20% mannitol were effective in reducing ICP(P ＜0.05).Therapeutic effect lasted(4.5±1.2) h in HS group and(3.2±1.5) h in mannitoi group.3% HS had a longer duration of action than marmitol(P＜0.05).At the time point of 2 hours after treatment,MAP and CPP of HS group increased more than those of mannitol group(P＜0.05).Conclusion Both 3% HS and 20% mannitol could rapidly decrease ICP.3% HS has a longer duration of action in reducing ICP than 20% mannitol.3% HS is more effective in stabilizing circulation and improving CPP than 20% mannitol.     

间断静脉滴注3%高渗盐水与20%甘露醇治疗小儿急性脑水肿的疗效对比

Objective To compare the clinical efficacy of 3% hypertonic saline with 20% mannitol in the treatment of acute brain edema in children.Methods Twenty children with acute brain edema were randomly divided into hypertonic saline(HS) group and mannitol group.HS group and mannitol group were given 3% HS solution or 20% mannitol respectively.Main outcome measurements included intracranial pressure(ICP),mean arterial pressure(MAP),central venous pressure(CVP),cerebral perfusion pressure (CPP),serum electrolytes,plasma osmolality,renal function and urine volume.Results Both 3% HS and 20% mannitol were effective in reducing ICP(P ＜0.05).Therapeutic effect lasted(4.5±1.2) h in HS group and(3.2±1.5) h in mannitoi group.3% HS had a longer duration of action than marmitol(P＜0.05).At the time point of 2 hours after treatment,MAP and CPP of HS group increased more than those of mannitol group(P＜0.05).Conclusion Both 3% HS and 20% mannitol could rapidly decrease ICP.3% HS has a longer duration of action in reducing ICP than 20% mannitol.3% HS is more effective in stabilizing circulation and improving CPP than 20% mannitol.     

间断静脉滴注3%高渗盐水与20%甘露醇治疗小儿急性脑水肿的疗效对比

Objective To compare the clinical efficacy of 3% hypertonic saline with 20% mannitol in the treatment of acute brain edema in children.Methods Twenty children with acute brain edema were randomly divided into hypertonic saline(HS) group and mannitol group.HS group and mannitol group were given 3% HS solution or 20% mannitol respectively.Main outcome measurements included intracranial pressure(ICP),mean arterial pressure(MAP),central venous pressure(CVP),cerebral perfusion pressure (CPP),serum electrolytes,plasma osmolality,renal function and urine volume.Results Both 3% HS and 20% mannitol were effective in reducing ICP(P ＜0.05).Therapeutic effect lasted(4.5±1.2) h in HS group and(3.2±1.5) h in mannitoi group.3% HS had a longer duration of action than marmitol(P＜0.05).At the time point of 2 hours after treatment,MAP and CPP of HS group increased more than those of mannitol group(P＜0.05).Conclusion Both 3% HS and 20% mannitol could rapidly decrease ICP.3% HS has a longer duration of action in reducing ICP than 20% mannitol.3% HS is more effective in stabilizing circulation and improving CPP than 20% mannitol.     

间断静脉滴注3%高渗盐水与20%甘露醇治疗小儿急性脑水肿的疗效对比

Objective To compare the clinical efficacy of 3% hypertonic saline with 20% mannitol in the treatment of acute brain edema in children.Methods Twenty children with acute brain edema were randomly divided into hypertonic saline(HS) group and mannitol group.HS group and mannitol group were given 3% HS solution or 20% mannitol respectively.Main outcome measurements included intracranial pressure(ICP),mean arterial pressure(MAP),central venous pressure(CVP),cerebral perfusion pressure (CPP),serum electrolytes,plasma osmolality,renal function and urine volume.Results Both 3% HS and 20% mannitol were effective in reducing ICP(P ＜0.05).Therapeutic effect lasted(4.5±1.2) h in HS group and(3.2±1.5) h in mannitoi group.3% HS had a longer duration of action than marmitol(P＜0.05).At the time point of 2 hours after treatment,MAP and CPP of HS group increased more than those of mannitol group(P＜0.05).Conclusion Both 3% HS and 20% mannitol could rapidly decrease ICP.3% HS has a longer duration of action in reducing ICP than 20% mannitol.3% HS is more effective in stabilizing circulation and improving CPP than 20% mannitol.     

间断静脉滴注3%高渗盐水与20%甘露醇治疗小儿急性脑水肿的疗效对比

Objective To compare the clinical efficacy of 3% hypertonic saline with 20% mannitol in the treatment of acute brain edema in children.Methods Twenty children with acute brain edema were randomly divided into hypertonic saline(HS) group and mannitol group.HS group and mannitol group were given 3% HS solution or 20% mannitol respectively.Main outcome measurements included intracranial pressure(ICP),mean arterial pressure(MAP),central venous pressure(CVP),cerebral perfusion pressure (CPP),serum electrolytes,plasma osmolality,renal function and urine volume.Results Both 3% HS and 20% mannitol were effective in reducing ICP(P ＜0.05).Therapeutic effect lasted(4.5±1.2) h in HS group and(3.2±1.5) h in mannitoi group.3% HS had a longer duration of action than marmitol(P＜0.05).At the time point of 2 hours after treatment,MAP and CPP of HS group increased more than those of mannitol group(P＜0.05).Conclusion Both 3% HS and 20% mannitol could rapidly decrease ICP.3% HS has a longer duration of action in reducing ICP than 20% mannitol.3% HS is more effective in stabilizing circulation and improving CPP than 20% mannitol.     

间断静脉滴注3%高渗盐水与20%甘露醇治疗小儿急性脑水肿的疗效对比

Objective To compare the clinical efficacy of 3% hypertonic saline with 20% mannitol in the treatment of acute brain edema in children.Methods Twenty children with acute brain edema were randomly divided into hypertonic saline(HS) group and mannitol group.HS group and mannitol group were given 3% HS solution or 20% mannitol respectively.Main outcome measurements included intracranial pressure(ICP),mean arterial pressure(MAP),central venous pressure(CVP),cerebral perfusion pressure (CPP),serum electrolytes,plasma osmolality,renal function and urine volume.Results Both 3% HS and 20% mannitol were effective in reducing ICP(P ＜0.05).Therapeutic effect lasted(4.5±1.2) h in HS group and(3.2±1.5) h in mannitoi group.3% HS had a longer duration of action than marmitol(P＜0.05).At the time point of 2 hours after treatment,MAP and CPP of HS group increased more than those of mannitol group(P＜0.05).Conclusion Both 3% HS and 20% mannitol could rapidly decrease ICP.3% HS has a longer duration of action in reducing ICP than 20% mannitol.3% HS is more effective in stabilizing circulation and improving CPP than 20% mannitol.     

米诺环素对未成熟新生大鼠缺氧缺血性脑损伤的作用

目的 研究米诺环素(minocycline,MN)对未成熟新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)的作用.方法 生后2 d(P2)Sprague-Dawley(SD)大鼠192只,随机分成正常对照组、假手术组、HIBD组、HIBD+MN组,每组48只.通过结扎左侧颈总动脉及8%氮氧混合气缺氧4 h,制作未成熟新生大鼠缺氧缺血性脑损伤模型.假手术组只分离左侧颈总动脉,正常组未予任何处理.HIBD+MN组动物于HI后腹腔注射米诺环素45 mg/kg,此后2 d每24小时腹腔注射1次.HI后3 d,1、2、4周,行常规HE染色及病理评分,HI后3 d及2周,行抗O4、抗O1免疫组化及髓鞘脂碱性蛋白(MBP)免疫组化.HI后4周行神经行为学检测.结果 HIBD组病理可见脑室周围白质损伤,HIBD+MN组病变较轻;O4阳性细胞计数:HIBD+MN组与正常组差异无统计学意义,P＞0.05,而HIBD组较正常组,假手术组、HIBD+MN组减少,差异有统计学意义(23.67±12.00 vs 52.89±10.68,39.28±11.78,41.63±8.41,P＜0.05);O1阳性细胞计数:正常组,假手术组、HIBD组、HIBD+MN组组间差异无统计学意义,P=0.093;MBP阳性纤维束计数:HIBD+MN组与正常组、假手术组差别有统计学意义,P＜0.05,而HIBD组较正常组、假手术组、HIBD+MN组减少,差异有统计学意义(14.71 ±7.42 vs 36.67±6.50,35.50±3.24,26.33±5.92,P＜0.05);HIBD组HI后4周出现明显远期行为学异常,在斜坡试验、悬吊试验及Cylinder试验中,HIBD+MN组与正常组、假手术组差别无统计学意义,P＞0.05;HIBD组与正常组、假手术组及HIBD+MN组差异有统计学意义,P＜0.05;在旷场试验中,HIBD+MN组与HIBD组差异无统计学意义,P=0.772,两组与正常组,假手术组差异均有统计学意义,P＜0.05.结论 米诺环素对未成熟新生大鼠缺氧缺血性脑损伤有早期及远期保护作用.     

基于371例儿童紫癜性肾炎的临床与病理分型的相关性分析

目的探讨儿童紫癜性肾炎(HSPN)的临床和肾脏病理特点。方法回顾性分析2016年1月1日至2018年12月31日在河南中医药大学第一附属医院（我院）儿科住院、有肾活检病理报告、年龄＜18周岁的HSPN患儿的临床和病理资料。结果371例HSPN患儿进入本文分析,男223例、女148例,中位年龄10（2~18）岁。①85.4%患儿于皮肤紫癜后1个月内出现尿检异常。紫癜伴消化道和关节症状者占37.5%,紫癜伴关节、肌肉症状者占21.6%,紫癜伴消化道症状者占20.2%。②临床分型：血尿加蛋白尿型占78.4%,肾病综合征（NS）型占15.1%,单纯性蛋白尿型和单纯性血尿型各占3.2%。NS型（12.5%,7/56）较血尿加蛋白尿型（3.8%,11/291）中肉眼血尿比例较高（χ2=28.4,P＜0.01）。有消化道症状者（45.8%,98/214）较无消化道症状者大量蛋白尿的比例高（40.1%,63/157）（χ2=15.6,P＜0.001）。③光学显微镜分级以Ⅲ级最多（74.9%）,其中Ⅲa和Ⅲb型各占46.6%和28.3%,其次为Ⅱ型（21.3%）。免疫荧光分型以IgA型最多（83.3%）。④临床分型与光学显微镜分级（r=0.264,P＜0.001）和肾小管病理分级（r=0.246,P＜0.001）、光学显微镜分级与肾小管病理分级（r=0.366,P＜0.001）、新月体的比例与24 h尿蛋白量（F=3.980,P=0.001）均有相关性。结论儿童HSPN临床以血尿加蛋白尿型最常见,病理以Ⅱ级和Ⅲ级多见。临床与病理、消化道症状与大量蛋白尿、NS型和肉眼血尿、肾小管病变程度与病理分型、新月体含量与24 h尿蛋白水平等均有一定相关性。     

基于371例儿童紫癜性肾炎的临床与病理分型的相关性分析

目的探讨儿童紫癜性肾炎(HSPN)的临床和肾脏病理特点。方法回顾性分析2016年1月1日至2018年12月31日在河南中医药大学第一附属医院（我院）儿科住院、有肾活检病理报告、年龄＜18周岁的HSPN患儿的临床和病理资料。结果371例HSPN患儿进入本文分析，男223例、女148例，中位年龄10（2~18）岁。①85.4%患儿于皮肤紫癜后1个月内出现尿检异常。紫癜伴消化道和关节症状者占37.5%，紫癜伴关节、肌肉症状者占21.6%，紫癜伴消化道症状者占20.2%。②临床分型：血尿加蛋白尿型占78.4%，肾病综合征（NS）型占15.1%，单纯性蛋白尿型和单纯性血尿型各占3.2%。NS型（12.5%，7/56）较血尿加蛋白尿型（3.8%,11/291）中肉眼血尿比例较高（χ2=28.4，P＜0.01）。有消化道症状者（45.8%，98/214）较无消化道症状者大量蛋白尿的比例高（40.1%，63/157）（χ2=15.6，P＜0.001）。③光学显微镜分级以Ⅲ级最多（74.9%），其中Ⅲa和Ⅲb型各占46.6%和28.3%，其次为Ⅱ型（21.3%）。免疫荧光分型以IgA型最多（83.3%）。④临床分型与光学显微镜分级（r=0.264，P＜0.001）和肾小管病理分级（r=0.246，P＜0.001）、光学显微镜分级与肾小管病理分级（r=0.366，P＜0.001）、新月体的比例与24 h尿蛋白量（F=3.980，P=0.001）均有相关性。结论儿童HSPN临床以血尿加蛋白尿型最常见，病理以Ⅱ级和Ⅲ级多见。临床与病理、消化道症状与大量蛋白尿、NS型和肉眼血尿、肾小管病变程度与病理分型、新月体含量与24 h尿蛋白水平等均有一定相关性。     

百令胶囊对肾小管间质纤维化大鼠肾小管上皮-间质转分化的干预作用

目的探讨百令胶囊对小管间质纤维化大鼠小管上皮-间质转分化的干预作用。方法利用腺嘌呤诱导建立肾小管间质纤维化大鼠模型,实验SD大鼠随机分为模型组、干预组、对照组各30只,分别于实验第7周、12周、17周收获动物各10只,进行功能学和肾脏组织病理学检测和观察。利用免疫组织化学对骨形态发生蛋白-7(BMP-7)、转化生长因子-β1(TGF-β1)和α-平滑肌肌动蛋白(-αSMA)在肾小管间质纤维化大鼠中的表达变化进行动态观察及百令胶囊的干预影响。结果实验第7周模型组大鼠即表现出大量蛋白尿、小管损伤、间质的轻度纤维化和炎症细胞浸润(P<0.01);随病程进展,上述病变呈进行性加重(P<0.01)。百令胶囊干预组动物在实验第7周、12周功能学组织学的改善同实验组相比有明显差异(P<0.01),17周后二者无显著差异。免疫组织化学显示百令胶囊12周前能显著上调BMP-7的表达和降低-αSMA和TGF-β1在肾脏小管间质中的表达(P<0.01),12周后这种变化无差异。结论百令胶囊在发病早期通过有效干预上皮-间质转分化达到改善肾脏纤维化的作用,随着肾小管间质纤维化程度的加重,百令胶囊逐渐失去其阻断作用。     

水通道蛋白2在脓毒症大鼠肾脏的表达及意义

目的 探讨水通道蛋白2(AQP2)在脓毒症大鼠肾脏的表达及对水代谢调节的意义.方法 将6周龄Wistar大鼠64只,随机分为假手术组和手术组各32只,采用盲肠结扎穿孔法(CLP)复制脓毒症模型.每组分为3、6、12和24 h 4个亚组,各8只,分别留取尿液、血液、肾脏标本.观察尿量、尿渗透压和肾功能,HE染色光镜观察肾脏病理变化,采用实时定量PCR方法检测AQP2 mRNA表达,免疫组织化学方法检测AQP2的蛋白表达.结果 手术组大鼠术后3 h尿量减少、尿渗透压增高,6 h后尿量逐渐增多、尿渗透压降低;血肌酐和尿素6 h开始升高,24 h达高峰;随术后时间延长肾脏病理损害加重,主要表现为肾小管上皮细胞之间间隔消失,细胞核消失;肾小球球襻融合,细胞结构不清;间质可见点灶状炎性细胞侵润.AQP2 mRNA的表达在术后3 h增高,12、24 h明显减低;AQP2蛋白表达在术后12 h下降,24 h最低,较假手术组均有显著性差异(P<0.05).结论 AQP2参与脓毒症时肾脏水代谢的调节,AQP2表达下调导致脓毒症尿浓缩功能障碍的主要病理机制之一.     

过敏性紫癜患儿早期肾损害的实验室检查及干预

目的 探讨过敏性紫癜( Henoch-Schonlein purpura,HSP)患儿早期肾损害诊断的实验室指标及早期干预的临床疗效.方法 对143例多次尿常规检查正常的HSP患儿进一步检测尿微量蛋白[免疫球蛋白G(IgG)、微量白蛋白(MA)、转铁蛋白(TRF)、a1-微球蛋白(α1-MG)、β2-微球蛋白(β2-MG)]以及尿酶[N-乙酰-β-D氨基葡萄糖苷酶(NAG),y-谷氨酰转肽酶(y-GT)]的含量.采用对比研究方法,将131例检查异常的HSP患儿随机分成两组(对照组65例、干预组66例).两组均给予甲氰咪胍、氯雷他定、钙剂等综合治疗,干预组66例在综合治疗的基础上加用小剂量肝素微量泵持续定时静脉滴注及甘利欣口服治疗,对照组65例未给予其他治疗.结果 143例尿常规检查正常的HSP患儿中尿微量蛋白和尿酶异常131例(91.61％),干预组治疗2个月、4个月尿微量蛋白、尿酶各项指标均较治j前降低,差异有统计学意义(P＜0.01).对照组治疗2个月仅尿β2-MG、NAG、y-GT 3项指标降低,差异有统计学意义(P＜0.01),治疗4个月尿微量蛋白、尿酶各项指标均较治疗前降低,差异有统计学意义(P＜0.01).干预组治疗2个月、4个月尿微量蛋白、尿酶各项指标均较对照组低,差异有统计学意义(P ＜0.05或P＜0.01).尿IgG、MA、TRF 、NAG恢复较快,干预组治疗4个月时已基本接近正常,而尿α1-MG、β2-MG、γ-GT恢复较慢,干预组治疗4个月时仍有轻重不一的异常.两组治疗4个月时,对照组尿常规异常率高于干预组(36.92％ vs 6.10％),差异有统计学意义(P＜0.05).结论 尿微量蛋白及尿酶7项指标的联合检测是早期诊断HSP肾损害的良好指标.应用肝素钠、甘利欣对其进行早期干预,能有效预防肾损害,延缓疾病进展.对HSP肾损害须强调早期诊断及早期干预.     

缺氧缺血后新生鼠脑组织caspase-3mRNA表达变化及其意义

目的　观察新生大鼠缺氧缺血后脑组织caspase 3mRNA表达动态变化 ,进一步探讨缺氧缺血诱导新生鼠神经元凋亡的机制及意义。方法　制备新生鼠HIBD模型 ,随机分为假手术对照组、HIBD 6h、2 4h、3d、5d组 ,每组 5只动物。应用RT PCR方法测定了大鼠脑组织caspase 3mRNA的表达。结果　 7日龄Wistar大鼠假手术对照组即有一定水平caspase 3mRNA表达 ,HIBD 6h组表达增加(与对照组比较有显著性差异 ,P <0 0 5 ) ,HIBD 2 4h其表达呈高峰 ,此后逐渐下降 ,HIBD 5d仍维持较高水平 (与HIBD 6h相比有显著性差异 ,P <0 0 1)。结论　缺氧缺血可诱导新生鼠脑组织caspase 3mRNA表达 ,其过度表达在HIBD后神经元凋亡的调控中起一定作用 ,针对caspase 3的治疗对策为围生期缺氧缺血脑损伤打开了新视窗     

喹那普利对单侧输尿管结扎大鼠肾纤维化拮抗作用的研究

目的 研究喹那普利对梗阻性肾病肾间质纤维化的影响及其机制。方法 30只SD大鼠随机分为3组：假手术组（n＝6）、单侧输尿管结扎(UUO)组（n＝12）和喹那普利组（n＝12）。喹那普利组在UUO术前1 d予喹那普利10 mg·kg-1·d-1 灌胃,假手术组及UUO组予同等体积生理盐水灌胃。各组大鼠分别于术后14和28 d取梗阻侧肾组织。采用Masson染色及免疫组化方法观测各组大鼠的肾间质容量、肾组织α-平滑肌肌动蛋白（α-SMA）及转化生长因子-β1（TGF-β1）蛋白水平的变化。以原位杂交法检测各组大鼠肾组织TGF-β1 mRNA表达的变化。结果 与假手术组比较,UUO组大鼠肾小管明显萎缩塌陷或极度扩张,伴肾间质增生,输尿管梗阻后4周时上述病理改变尤为明显,肾间质容量明显升高(P<0.001)。免疫组化染色检测结果显示,UUO组α-SMA及TGF-β1蛋白水平均明显高于假手术组,且随梗阻时间的延长呈进行性升高(P<0.001)。原位杂交结果表明,UUO组TGF-β1 mRNA在肾小管间质中的表达显著高于假手术组(P<0.001)。喹那普利组肾间质容量、肾小管间质中TGF-β1 mRNA表达、TGF-β1蛋白和α-SMA水平均显著低于UUO组(P<0.05或<0.01)。结论 喹那普利可明显抑制肾组织分泌TGF-β1,可能的机制之一是减少其下游效应细胞-肌纤维母细胞的活化,从而减缓UUO大鼠肾纤维化进程。     

针刺对缺氧缺血性脑病模型大鼠哺乳动物雷帕霉素靶蛋白的干预研究

目的：观察针刺对缺氧缺血性脑病模型大鼠哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)的干预作用。方法7日龄 SD 大鼠按区组随机法随机分为6组。假手术组：分离双侧颈总动脉不结扎,不做低氧处理;模型组：分离双侧颈总动脉并结扎,置于低氧气体中,不行干预;假针刺组：缺氧缺血后进行针刺,针刺位点距“百会”、“大椎”、“曲池”、“涌泉”四穴旁开1 cm 处;针刺组：缺氧缺血后第2天针刺“百会”、“大椎”、“曲池”、“涌泉”四穴;拮抗剂组：缺氧缺血后幼鼠左侧脑室注射渥曼青霉素5μl,不行干预;针刺加拮抗剂组：缺氧缺血后幼鼠左侧脑室注射渥曼青霉素5μl,其他方面同针刺组。每组又分为1 d、3 d、7 d、21 d 四个亚组,观察大鼠缺氧缺血侧脑组织的形态学变化,RT-PCR 方法检测 mTOR mRNA 的表达。结果病理结果显示,21 d 时针刺组神经细胞肿胀变轻,排列有序,可见胶质细胞增生,细胞轮廓及核仁较清晰。与模型组比较,针刺组1 d、3 d、7 d、21 d mTOR mRNA 均表达增加,差异有统计学意义(Q 值分别为7.0991,9.0099,7.8940,9.9147,P ﹤0.05)。针刺加拮抗剂组中,1 d、3 d、7 d 时 mTOR mRNA 的表达与假手术组比较,差异有统计学意义(Q 值分别为9.8689,15.8434,21.0072,P ﹤0.05),至21 d 时,与假手术组及模型组比较差异均有统计学意义(Q =18.2360,Q =4.7297,P 均﹤0.05)。结论针刺能够促进 mTOR mRNA 的表达,对缺氧缺血性脑病大鼠发挥较好的脑保护作用。