大鼠慢性肾功能不全模型两种制作方式的比较

目的比较大鼠肾大部切除与肾结扎两种方法制备的5／6肾切除慢性肾功能不全模型的异同。方法雄性SD大鼠随机分为三组。A组行左肾2／3切除加右肾切除,B组行结扎左肾动脉2／3分支加右肾切除,C组为假手术组。分别于第二次手术后5周、9周及13周测血压,处死大鼠,留取24h尿及肾组织。检测尿蛋白,肾组织切片染色。用半定量法评价肾小球硬化指数。结果第5周时,B组大鼠的收缩压显著升高,而A组与C组相比无显著差异,第9周和13周A组和B组与C组大鼠相比,收缩压均显著升高。肾部分切除术后,尿蛋白随时间进行性增加。B组与A组相比,尿蛋白增加更为显著。A组和B组在各观察点均有不同程度肾小球硬化,B组较A组肾小球硬化程度重。结论肾大部切除和肾结扎两种方法制备的大鼠5／6肾切除模型表现有所不同。     

慢性肾衰竭大鼠模型的建立

目的 建立两种慢性肾衰竭大鼠模型,观察瘦素蛋白在大鼠组织、器官中的表达.方法 建立两种慢性肾衰竭CRF动物模型:(1)大鼠肾大部分切除诱发肾衰(Platt法).(2)腺嘌呤诱发大鼠慢性肾衰竭的动物模型(Yokozawa法).分别测定血清中血尿素氮(BUN),血肌酐(Scr)Ca2+、P5+等含量.取肾脏组织,HE染色,行免疫荧光,检测瘦素蛋白在两种慢性肾衰竭大鼠模型中的表达情况.结果 模型组大鼠血清中血尿素氮(BUN),血肌酐(Scr)等含量明显升高,免疫荧光检测显示两种模型大鼠肾脏组织瘦素蛋白的表达.结论 成功建立两种慢性肾衰竭CRF动物模型,显示不同模型组织部位的瘦素蛋白的表达.为进一步探讨瘦素蛋白在动物体内的生物学作用提供实验基础.     

应用高脂饮食联合维生素D3建立慢性系膜增殖性肾炎血管病变大鼠模型

目的 探讨应用高脂饮食建立慢性系膜增殖性肾炎血管病变模型的方法.方法 雄性Wistar大鼠行单侧肾切除后随机分为单纯肾切除组、单纯肾炎组、单纯高脂组、肾炎高脂组.单纯肾炎组、肾炎高脂组在单侧肾切除后3d尾静脉注射OX7抗体(100 mg/kg),1周后尾静脉连续注射OX7抗体(每次100 mg/kg,1次/周,共3次),单纯肾切除组和单纯高脂组在同一时间尾静脉注射PBS,注射抗体后第2天单纯高脂组、肾炎高脂组腹腔注射维生素D3(6万U/kg,1次/4周),同时给予高脂饲料.分别于第4、8、10周观察各组大鼠的一般情况、体重、血压、尿蛋白、血浆白蛋白、血脂、血钙、肾功能以及肾脏病理改变.结果 模型组(肾炎高脂组)大鼠第8周肾小球外的小动脉出现管壁增厚,管腔变小,平滑肌细胞减少,细胞排列紊乱,纤维组织增生.第10周单纯肾炎组和单纯高脂组肾小球外小动脉管壁轻度增厚,管腔变化不明显,模型组血管病变积分明显高于单纯肾炎组和单纯高脂组(P＜0.05).结论 通过对慢性抗Thy1肾炎大鼠加用高脂饲料并腹腔注射维生素D3的方法,可以成功建立慢性系膜增殖性肾炎血管病变模型.     

改良半椎板切除法建立大鼠腰神经根压迫模型

目的探讨改良半椎板切除法建立大鼠腰神经根压迫模型的优势和特点。方法选用SD大鼠40只,随机分为实验组和对照组,实验组采用改良半椎板切除法建立大鼠腰神经根压迫模型,对照组则采用全椎板切除法,通过观察两组建模手术时间、术中出血量、伤口愈合情况、死亡率、大鼠下肢神经功能、神经根组织病理改变及TNF-α及IL-1在细胞质中灰度值表达水平评估两种方法的效果。结果实验组在建模手术时间、术中出血量、伤口愈合状况、死亡率明显少于对照组(P0.01),而大鼠下肢神经功能、神经根组织病理改变及TNF-α及IL-1在细胞质中灰度值表达水平无明显差异,同时,实验组所需的切口小,脊柱后方软组织破坏少。结论采用改良半椎板切除法可保证成功建立大鼠腰神经根压迫模型,并且这一改良方法具有手术时间短,伤口愈合快,出血量少,软组织破坏少,死亡率低等优点,这一改良方法更注重动物伦理。     

Ang Ⅱ拮抗剂对慢性肾衰大鼠肾血流量和肾内氧耗的影响

目的观察血管紧张素II(AngⅡ)拮抗剂对5/6(ablation/infarction,A/I)肾切除诱导慢性肾衰竭(CRF)大鼠肾功能、肾血流量及肾内氧耗的影响。方法制备5/6(A/I)肾切除诱导慢性肾衰大鼠模型,设正常组(A组,n=14只),模型组(B组,n=14只),AngⅡ拮抗剂治疗组(氯沙坦钾联合福辛普利钠)(C组,n=14只)。给予相应干预,疗程60 d。分别测量尾动脉收缩压(SBP)、舒张压(DBP),检测大鼠尾静脉血清肌酐(Scr)、尿素氮(BUN)、血红蛋白(Hb),计算内生肌酐清除率(Ccr)。干预60 d后,检测肾血流量(RBF)、腹主动脉和肾静脉血气(AABG and RVBG),左肾静脉压(RVpO2),计算残余肾内氧耗(QO2/TNa)及观察残肾组织病理变化。结果 (1)造模后与A组比较,B、C两组的Scr、BUN和尾动脉SBP、DBP显著增加(P0.01),Ccr、Hb显著降低(P0.01),提示造模成功。(2)干预后与B组比较,C组的Scr、尾动脉SBP、DBP、QO2/TNa明显下降(P0.01),BUN降低(P0.05),Hb、Ccr、RVpO2显著升高(P0.01),RBF升高(P0.05)。(3)残肾组织病理形态学变化显示,C组的肾组织病理变化明显减轻,优于B组。结论 AngⅡ拮抗剂可以增加慢性肾衰大鼠肾血流量,降低肾内氧耗,改善肾功能及减轻肾组织病理变化,其肾脏保护作用机制可能与其调节细胞能量代谢,改善肾内氧耗有关。     

大鼠5/6肾切除慢性肾功能衰竭动物模型的实验研究

观察5/6肾切除大鼠模型中肾功能、肾脏病理改变、肾组织α-平滑肌肌动蛋白(α-SMA)表达的变化,证明5/6肾切除可制作理想的慢性肾功能衰竭、肾间质纤维化动物模型。方法:大鼠随机分为假手术组(SOR)和5/6肾切除组。随机选取各组中的10只大鼠分别于5/6肾切除术后30、60和90天处死,收集血清与肾组织供生化及病理分析。结果:①5/6肾切除组24小时尿蛋白定量、血尿素氮、血肌酐水平明显高于假手术组(P<0.05)。②残肾的肾重/体重逐渐增加,到术后90天时,几乎接近假手术组大鼠左肾肾重/体重。③5/6肾切除后,残肾肾小球面积和肾小球毛细血管体积增加,肾小球硬化指数(GSI)及肾小管间质损伤评分(TIS)明显高于假手术组(P<0.05)。④免疫组化结果显示,5/6肾切除组肾间质和小管上皮细胞α-SMA表达增加。⑤肾小球面积、GSI、α-SMA表达与血肌酐、蛋白尿水平呈明显正相关性。结论:5/6肾切除可以建立伴慢性肾功能衰竭的肾间质纤维化动物模型。     

大黄酸和迷迭香酸单用及配伍对慢性肾脏疾病的保护作用研究

目的:探讨大黄酸和迷迭香酸单用及配伍通过抗凋亡对5/6肾切除(5/6Nx)大鼠的保护作用。方法:采用5/6肾切除手术制作慢性肾损伤模型,将30只雄性SD大鼠随机分为假手术组、模型组、大黄酸(150 mg/kg/day)治疗组、大黄酸(75mg/kg/day)+迷迭香酸(75 mg/kg/day)治疗组和迷迭香酸(150 mg/kg/day)治疗组。给药1个月后处死大鼠,测量各组大鼠血清肌酐(Scr)和尿素氮(BUN)水平,通过HE染色观察肾组织形态学变化,通过TUNEL染色和测量肾组织中Bax、Bcl-2和cleaved caspase 3的表达检测细胞凋亡。结果:与模型组相比,大黄酸和迷迭香酸单用及配伍都可显著降低血清肌酐和尿素氮(P0.05)水平,改变组织形态学的变化和抑制肾脏细胞凋亡,且配伍的效果优于单用。结论:大黄酸和迷迭香酸配伍发挥肾保护作用明显优于单用,其作用机制与抗凋亡作用相关。     

树突状细胞在肾小管间质纤维化中作用及缬沙坦的干预调节

探讨树突状细胞(DC)在肾纤维化大鼠肾小管间质中分布,以及缬沙坦对DC浸润聚集的干预作用。建立肾大部切除大鼠模型,随机分为正常组(n=18),假手术组(n=18),模型组(n=18),缬沙坦治疗组(n=18)。分别于建模1、4、12周取肾组织,采用HE和Masson染色评定各组肾小管间质纤维化(TIF)程度;采用免疫双染及荧光图像分析法,观察DC-SIGN DC在各组大鼠肾组织中分布变化;采用免疫组化方法,观察P-选择素以及TGF-β1、α-平滑肌肌动蛋白(α-SMA)、III型胶元(ColIII)、纤维连接蛋白(FN)在上述肾组织中表达;以及RT-PCR检测P-选择素、TGF-β1、α-SMA、ColIII、FN的mRNA水平。结果显示,(1)模型组DC-SIGN DC主要分布于肾小管、肾间质和肾血管,以肾间质最为明显;其分布数量于12周较1和4周呈明显增多,且与慢性肾功能减退呈正相关。(2)12周时手术组大鼠肾小管间质区P-选择素、TGF-β1、α-SMA、ColIII、FN mRNA转录水平和蛋白质表达均明显增加,并与TIF程度以及DC-SIGN DC分布数量呈正相关。(3)经缬沙坦治疗后,DC-SIGN DC分布减少,以及P-选择素、TGF-β1、α-SMA、ColIII、FN mRNA转录水平和蛋白质表达下降,TIF程度减轻及肾功能改善。研究结果表明,DC启动参与了肾小管间质纤维化形成,并与肾功能损害程度密切相关。缬沙坦对此具有明显的抑制和肾脏保护作用。     

肾大部切除,高盐摄食对SD大鼠脑心房钠尿钠的影响

为探讨脑内心房钠尿肽（ＡＮＰ）的作用,本工作采用ＳＤ大鼠,用放射免疫方法测定３／４肾大部切除与高盐摄食后脑内ＡＮＰ的含量。。结果表明,对照组大鼠脑内ＡＮＰ分布广泛。３／４肾切除大鼠每日饮水量尿量均比对照组高（Ｐ〈０．０５）,尿钠浓度低于对照组时,脑内ＡＮＰ含量尽管略有增加,但１０个核团（下丘脑室周核、弓状核、室旁核、视前室周核、中缝背核、高盐摄食组每日饮水量和尿量均比对照组高,且尿钠浓度高于对照缄     

硬膜外导管在大鼠肾移植血管吻合中的应用

目的建立一种手术难度低,成功率高的大鼠肾移植模型。方法 Wistar大鼠作供体,SD大鼠作受体,将供体腔静脉与受体肾静脉端端吻合,供体腹主动脉与受体腹主动脉端侧吻合,供体膀胱瓣与受体膀胱吻合。根据血管吻合时应用硬膜外导管与否,将受体分为有支架组和无支架组两组。结果有支架组共进行肾移植30次,成活26只;无支架组共进行肾移植20次,成活10只。有支架组的成活率86.7%（26/30）较无支架组50.0%（10/20）明显提高（P〈0.05）,血管吻合总时间（22±2）min较无支架组（32±2）min明显缩短（P〈0.05）。结论硬膜外导管应用于大鼠肾移植血管吻合,降低了手术难度,减少了吻合口出血,提高了手术成功率。     

P-P42/p44在慢性肾功能不全大鼠肾组织表达特征及其作用

目的探讨慢性肾功能不全大鼠肾组织磷酸化P42/p44丝裂原活化蛋白激酶(P-P42/p44 MAPK)的表达特征及其可能的作用。方法16只Wistar大鼠随机分成实验组和对照组,每组8只。采用5/6肾切除方法构建慢性肾功能不全大鼠模型,术后120d处死大鼠,取大鼠肾组织行石蜡切片,PAS染色观察大鼠肾脏病理改变,免疫组化和Western blot法分别检测大鼠肾组织磷酸化P42/p44丝裂原活化蛋白激酶的表达特征及活性变化。结果术后120d实验组大鼠与对照组相比,出现明显的肾小球硬化和肾小管坏死等慢性肾功能不全的典型病理特征,免疫组织化学染色检测磷酸化p42/p44 MAPK黄棕色染色颗粒明显增加。Western-blot结果显示,实验组大鼠肾组织磷酸化P42/p44丝裂原活化蛋白激酶(P-P42/p44 MAPK)活性表达水平明显上调(P<0.01)。结论磷酸化P42/p44丝裂原活化蛋白激酶在慢性肾功能不全大鼠模型的肾组织中活性明显升高,可能是慢性肾功能不全时各种细胞外刺激因素介导肾脏纤维化的重要途径之一。     

Content of Minerals and Fatty Acids and Their Correlation with Phytochemical Compounds and Antioxidant Activity of Leguminous Seeds

This study was carried out to determine the effect of zinc on oxidative DNA damage in rats with experimental acute and chronic kidney deficiency. Six groups of five Wistar-Albino rats each were assigned as controls (C), acute kidney deficiency (AKD), zinc-supplemented (+Zn), acute kidney deficiency, zinc-supplemented (AKD + Zn), chronic kidney deficiency (CKD) and zinc-supplemented chronic kidney deficiency (CKD + Zn). The levels of 8-Oxo-2′-deoxyguanosine (8-OHdG) were determined, being the lowest in the CKD group (p < 0.05), higher in the C group than those of rats with CKD but lower than that of all the other groups (p < 0.05). There were no significant differences between the controls and the CKD + Zn group, or between the AKD and the +Zn groups. Among all groups, the highest 8-OHdG level was found in the AKD + Zn group (p < 0.05). DNA damage was greater in acute renal failure than in rats with chronic renal failure. The DNA damage in the zinc group was significantly higher than in the controls.     

慢性肾缺血致心功能不全时大鼠心肌组织降钙素基因相关肽含量的变化

目的观察慢性肾缺血导致心功能不全时心肌组织降钙素基因相关肽（CGRP）含量变化,并分析变化的机制。方法将40只Wistar大鼠分为,狭窄对照组（n=15）和狭窄治疗组（n=15）,均采用两肾动脉之间腹主动脉缩窄术造成单侧慢性肾缺血。假手术组（n=10）仅分离腹主动脉。至术后16周狭窄治疗组给予阿魏酸钠40mg／kg腹腔内注射,狭窄对照组和假手术组均给予同等剂量生理盐水。治疗2周后,测定颈动脉压、左心功能,处死大鼠后测定心肌组织CGRP、ET-1和NO含量,分别测定心肌和脊髓背根神经节CGRP mRNA表达。结果狭窄对照组和狭窄治疗组心功能均下降,但狭窄治疗组心脏舒张功能优于狭窄对照组。狭窄对照组心肌内ET-1含量明显增加,CGRP含量明显下降。狭窄治疗组心肌内ET-1含量较对照组减少,CGRP含量略增高。各组心肌CGRP mRNA表达无明显差异。狭窄治疗组脊髓背根神经节CGRP mRNA表达较假手术组增加。结论大鼠慢性肾缺血导致心脏组织ET-1持续激活,CGRP、NO合成受损,与心功能下降密切相关。心功能不全时,脊髓背根神经节CGRP mRNA表汰代偿件增高,但心脏血管内皮绢织受损可能是心脏CGRP含量下降的主要因素。     

Is there any effect of renal failure on the hepatic regeneration capacity following partial hepatectomy in rats?

The effects of renal dysfunction on liver regeneration capacity have not been fully elucidated before, although many patients with renal failure are subjected to hepatectomy due to hepatobiliary diseases. In this study, we sought to determine the effects of renal dysfunction on the hepatic regeneration capacity using rat chronic renal failure model. After establishing chronic renal failure (CRF group) by semi-total renal resection, the rats were subjected to 70% partial hepatectomy (PHx). Rats without renal failure were used as control (Sham group). The hepatic regeneration rate, histology of the liver, clearance of indocyanine green into the bile, and the expression of hepatic regeneration-associated genes in the liver were evaluated. The hepatic regeneration rate was lower in CRF group as compared to Sham group on day 1 after PHx. Mitotic index evaluated by histologic examination on day 1 after PHx was also significantly lower in CRF group. However, no difference in these indices was observed on day 2 and 7 between Sham and CRF. Indocyanine green clearance rate was almost identical between Sham and CRF on day 7 following PHx. The baseline expressions of the hepatic regeneration-associated genes, such as IL-6, TNF-alpha, HGF, c-fos, and c-jun, in the liver of CRF were significantly lower than those of Sham. However, the rate of upregulation of these genes was not significantly different between Sham and CRF. These results clearly demonstrate that the renal dysfunction, although initially delays the onset, does not suppress the total hepatic regeneration capacity following partial hepatectomy. The function of the regenerated liver on day 7 after PHx also was not different. Our results provide a possibility that the hepatectomy can be indicated even for the patient with a chronic renal failure.     

Altered Orcadian Rhythms of Blood Pressure and Heart Rate in Non-Hemodialysis Chronic Renal Failure

The extended use of ambulatory monitoring has permitted the identification of many conditions in which the circadian rhythm of blood pressure is altered. The common denominator seems to be an impairment of the autonomic nervous system function. We examined whether the circadian blood pressure rhythm is altered in chronic renal failure (where autonomic dysfunction is usually present) by using a standardized chronobiological inferential statistical method in hospitalized subjects. For this purpose, a group of 30 non-hemodialysis hypertensive patients with chronic renal failure was compared with a second group of 30 patients affected by uncomplicated mild-to-moderate essential hypertension. The two groups were matched by age, sex and circadian mesors of blood pressure. Diet, meal times, sleep and activity logs were standardized. Blood pressure and heart rate recordings were obtained by using an automatic oscillometric recorder and subsequently analyzed according to the cosinor method. A mean circadian rhythm of blood pressure was documented in both groups, but while the mean acrophases occurred between 2 and 3 p.m. in essential hypertension, in renal failure they were between 11 p.m. and midnight for blood pressure and around 7 p.m. for heart rate. In addition, the mean circadian amplitudes were significantly lower in renal failure, while the mean circadian mesor of heart rate was significantly higher. Our data demonstrate that the circadian rhythms of blood pressure and heart rate are altered also in hypertension due to chronic renal failure.     

Altered Orcadian Rhythms of Blood Pressure and Heart Rate in Non-Hemodialysis Chronic Renal Failure

The extended use of ambulatory monitoring has permitted the identification of many conditions in which the circadian rhythm of blood pressure is altered. The common denominator seems to be an impairment of the autonomic nervous system function. We examined whether the circadian blood pressure rhythm is altered in chronic renal failure (where autonomic dysfunction is usually present) by using a standardized chronobiological inferential statistical method in hospitalized subjects. For this purpose, a group of 30 non-hemodialysis hypertensive patients with chronic renal failure was compared with a second group of 30 patients affected by uncomplicated mild-to-moderate essential hypertension. The two groups were matched by age, sex and circadian mesors of blood pressure. Diet, meal times, sleep and activity logs were standardized. Blood pressure and heart rate recordings were obtained by using an automatic oscillometric recorder and subsequently analyzed according to the cosinor method. A mean circadian rhythm of blood pressure was documented in both groups, but while the mean acrophases occurred between 2 and 3 p.m. in essential hypertension, in renal failure they were between 11 p.m. and midnight for blood pressure and around 7 p.m. for heart rate. In addition, the mean circadian amplitudes were significantly lower in renal failure, while the mean circadian mesor of heart rate was significantly higher. Our data demonstrate that the circadian rhythms of blood pressure and heart rate are altered also in hypertension due to chronic renal failure.     

实验性肾功能衰竭大鼠血浆中分子物质总量和自由基的变化研究

用腺嘌呤复制动物性慢性肾功能衰竭（ＣＲＦ）模型。观察大鼠血浆血尿素氮（ＢｕＮ）、血肌酐（Ｃｒ）、血红蛋白（Ｈｂ）、超氧化物歧化酶（ＳＯＤ）和中分子物质（ＭＭＳ）总量的变化。结果表明,ＣＲＦ大鼠血浆ＢｕＮ、Ｃｒ和ＭＭＳ总量明显升高（Ｐ〈０．０１）、Ｈｂ和ＳＯＤ含量显著降低（Ｐ〈０．０１）。提示ＣＲＦ大鼠ＭＭＳ总量升高、ＳＯＤ活性降低。     

Reference values of selenium in plasma in population from Barcelona. Comparison with several pathologies

Plasma selenium reference values from healthy donors in the metropolitan area of Barcelona are determined. A random sample from 156 healthy adults (control group) is analysed by using electrothermal atomic absorption spectrometry with Zeeman effect background correction.

The relationship between several pathologies and Se content is also evaluated. Se content from 64 samples from subjects with chronic renal failure and 54 from subjects suffering from several malignancies are determined and the results are compared to the reference values. Moreover, Se contents are determined and compared in two groups of children, healthy (19 samples) and children of mothers infected with HIV-1 (16 samples).

In the control group, Se plasma concentration ranges between 50 and 145 μg · L⁻¹ (82.2 ± 17.5 μg · L⁻¹). Significantly lower values are found in the two pathologies studied (malignancy and chronic renal failure), compared to the control group. However, no significant differences in Se content are found between the two groups studied regarding malignancy and chronic renal failure.

In children of mothers infected with HIV-1, Se status is significantly lower than that of healthy children.     

益肾活血汤联合百令胶囊对慢性肾功能衰竭患者肾功能、钙磷代谢和T淋巴细胞亚群的影响

摘要 目的：探讨益肾活血汤联合百令胶囊对慢性肾功能衰竭患者肾功能、钙磷代谢和T淋巴细胞亚群的影响。方法：选取2020年5月~2022年3月期间上海中医药大学附属曙光医院收治的102例慢性肾功能衰竭患者,按随机数字表法分为对照组（常规西医治疗）和观察组（常规西医治疗联合益肾活血汤和百令胶囊治疗）,各51例。两组均治疗8周。对比两组疗效及治疗前、治疗8周后中医证候积分、肾功能、钙磷代谢和T淋巴细胞亚群的变化。结果：观察组治疗8周后的临床总有效率为92.16%（47/51）,高于对照组的74.51%（38/51）（P<0.05）。治疗8周后,两组中医主证积分、次证积分均较治疗前下降,且相比于对照组,观察组更低（P<0.05）。治疗8周后,血肌酐、尿素氮、24 h尿蛋白在两组中均较治疗前下降,且观察组低于对照组（P<0.05）。治疗8周后,两组CD8⁺较治疗前下降,且观察组低于对照组（P<0.05）,而CD4⁺、CD3⁺、CD4⁺/CD8⁺均较治疗前升高,且观察组高于对照组（P<0.05）。治疗8周后,两组血磷、钙磷乘积下降,且观察组低于对照组（P<0.05）,血钙均升高,且观察组高于对照组（P<0.05）。结论：益肾活血汤联合百令胶囊治疗慢性肾功能衰竭患者,可提高肾功能,改善钙磷代谢和T淋巴细胞亚群,并缓解其临床症状,疗效确切,值得临床借鉴应用。