周脂素在糖尿病肾病大鼠肾组织中的表达

目的观察大鼠糖尿病肾病(diabetic nephropathy,DN)模型的特点和尿LN对早期DN的诊断价值,探讨周脂素(perilipin,Plin)在DN大鼠肾脏中的表达情况。方法将14只SD雄性大鼠随机分为对照组(普通饲料)和糖尿病肾病模型组(高糖高脂饲料),对照组6只,模型组8只,饲养4周后模型组按照30mg/kg剂量注射1%链脲佐菌素(STZ),检测血糖≥16.7mmol/L,糖尿病模型制作成功,继续喂养6周,检测24h尿蛋白≥30mg/kg,糖尿病肾病模型制作成功。考马斯亮蓝检测24h尿蛋白、ELISA测尿层粘连蛋白,HE染色观察肾组织的病理变化,Real-time PCR及Western blot检测肾脏组织中perilipin表达情况。结果模型鼠24h尿蛋白≥30mg/kg,糖尿病肾病大鼠模型制作成功。和对照组大鼠相比,模型组的肾重/体重比明显增高(P<0.05),尿量、尿层粘连蛋白于5周出现升高、24h尿蛋白于6周时出现升高,且三项指标均随着时间不断增高。肾组织病理检查显示:肾小球肥大,基膜增生,微小血管瘤形成,肾小管管腔变形,上皮脱落、空泡样变,大量单核、淋巴等炎性细胞浸润,间质内胶原纤维增生。模型组大鼠肾组织Plin的mRNA及蛋白表达均明显的升高(P<0.05)。结论尿层粘连蛋白比24h尿蛋白升高得早,可作为早期糖尿病肾病的警示指标。Plin表达增高可能参与了糖尿病肾病肾病变过程,为进一步探讨糖尿病肾病的发病机制提供新的思路。     

随机尿、晨尿视黄醇结合蛋白对早期肾功能损伤的诊断价值

目的:探究随机尿、晨尿视黄醇结合蛋白对早期肾功能损伤的诊断价值.方法:选取我院2011年8月-2012年9月收治的48例Ⅱ型糖尿病患者,按照随机数字表进行平均分组,随机尿组24例,选取任意时段尿液标本,晨尿组24例,选取清晨时段尿液标本.对两组患者尿液标本进行尿视黄醇结合蛋白(Urinary Retinol-binding Protein,U-RBP)、尿微量白蛋白(Urinary Microalbum, U-mAlb)及尿N-乙酰-β-D氨基葡萄糖苷酶(Urinary N-acetyl beta-D-Glucosaminidase,NAG)水平测定,进行相关性分析并观察两组诊断阳性率.结果:随机尿组U-RBP、U-mAlb及NAG分别为(1.7± 0.9) mg/L、(76.2± 41.5) mg/L及(41.2± 30.0) U/L;晨尿组U-RBP、U-mAlb及NAG分别为(3.6±1.2)mgL、(118.5±71.)mg/L及(116.5±71.9) U/L.两组患者尿液检测指标均高于正常值,且晨尿组指标较随机尿组更高,两组数据对比存在统计学差异;随机尿组U-RBP、U-mAlb及NAG阳性例数分别为12例、6例及4例,晨尿组U-RBP、U-mAlb及NAG阳性例数分别为17例、13例及11例,晨尿组U-RBP、U-mAlb及NAG阳性率均高于随机尿组,两组数据对比存在统计学差异;随机尿组U-RBP与肾损伤相关性r=0.532,P ＞0.05,无明显相关性;晨尿组U-RBP与肾损伤相关性r=0.867,P＜0.01,呈高度正相关.结论:随机尿及晨尿均可指示患者肾损伤出现,但随机尿蛋白指标无法有效指示肾损伤程度,对早期肾功能损害确诊准确率有限,而晨尿尿蛋白正常排泄率更高,且能够有效指示肾损伤程度,适用于糖尿病早期肾功能损伤的诊断及监测.     

尿蛋白定性与定量检测结果的差异性和相关性分析

目的:探讨尿液干化学法及免疫透射比浊法检测尿白蛋白结果的差异性及相关性。方法:对514例住院患者随机尿标本进行尿液干化学法及免疫透射比浊法尿蛋白的检测。结果:尿液干化学法阳性率为82.1%,免疫透射比浊法阳性率为72.8%。两种方法检测结果均为阴性标本的符合率为98.9%,为(±)的标本二者符合率为69.7%,为(+)的标本二者符合率为75.6%,为(++)的标本二者符合率为67.2%,为(+++)标本中二者符合率为42.5%,为(++++)标本二者的符合率为37.5%。两种方法的检测结果有显著性差异(P0.05);UmAlb/Ucr、NAG、和NAG/Ucr与UmAlb具有显著相关(P0.05),且UmAlb/Ucr与UmAlb的相关性最高。两种方法所得等级结果比较,++~+++之间差异有统计学意义(P0.05),-~±、±~+、+~++、+++~++++之间差异均无统计学意义(P0.05)。结论:尿蛋白定性与定量检测结果存在显著性差异,而UmAlb/Ucr与UmAlb相关性较高。在泌尿系统疾病的诊断中,检测尿中UmAlb比尿常规更有意义。     

高龄老年尿钠排泄的特点分析

目的:探讨高龄老年人24 h尿钠排泄特点,为防治老年钠代谢紊乱提供依据.方法:我院老年病房80岁以上老年42例,根据肌酐清除率分为肌酐清除率正常组及异常组.另选中年组24人及老年组31人作为对照.所有患者均检测24 h尿钠、钾、磷、肌酐及肌酐清除率.结果:①高龄组肌酐清除率低于中年组及老年组,24 h尿钠排泄量亦较中年组及老年组减少;高龄组中肌酐清除率异常组的24 h尿钠排泄量较肌酐清除率正常组显著减少.②中年组与老年组尿钠排泄和肌酐清除率无相关关系,高龄组尿钠排泄与肌酐清除有直线相关关系;高龄组肌酐清除率正常组肾脏排钾保钠能力减退、尿钠排泄增加,肌酐清除率异常组钾、钠排泄均减少;③三组的钠摄入量均在6g以上.结论:高龄老年24 h尿钠排泄与肌酐清除率呈直线相关关系.当肾功能处于代偿阶段时,钠排泄增多,但严重肾功能不全时尿钠排泄减少.     

不同分期慢性肾脏病患者血清Klotho蛋白、FGF-23、RBP4、TWEAK水平与肾功能的相关性研究

摘要 目的：探究不同分期慢性肾脏病(CKD)患者血清Klotho蛋白、成纤维细胞生长因子-23(FGF-23)、视黄醇结合蛋白4(RBP4)、肿瘤坏死因子样弱凋亡诱导因子(TWEAK)水平与肾功能的相关性。方法：选择2018年2月至2020年2月我院诊治的80例CKD患者作为CKD组,选择同期在我院进行健康体检的80名健康者作为对照组。检测并比较对照组和CKD组以及不同CKD分期患者血清Klotho蛋白、FGF-23、RBP4、TWEAK水平及肾功能指标水平,采用Pearson相关性分析对血清Klotho蛋白、FGF-23、RBP4、TWEAK水平与肾功能指标的相关性进行分析。结果：与对照组相比,CKD组血清Klotho蛋白、TWEAK水平和肾小球滤过率（GFR）明显下降,而血清FGF-23、RBP4水平、血清肌酐、24尿蛋白定量和血清尿素氮水平明显升高（P<0.05）。Ⅰ～Ⅱ期患者的血清Klotho蛋白、TWEAK水平和GFR最高,其次为Ⅲ～Ⅳ期患者,Ⅴ期患者最低（P<0.05）。而Ⅰ～Ⅱ期患者血清FGF-23、RBP4水平、血清肌酐、24尿蛋白定量和血清尿素氮水平最低,其次为Ⅲ～Ⅳ期患者,Ⅴ期患者最高（P<0.05）。Klotho蛋白和TWEAK水平与血清肌酐、24尿蛋白定量和血清尿素氮水平呈负相关,与GFR呈正相关（P<0.05）。FGF-23和RBP4水平与血清肌酐、24尿蛋白定量和血清尿素氮水平呈正相关,与GFR呈负相关（P<0.05）。结论：CKD患者中血清Klotho蛋白、TWEAK水平以及肾功能下降,FGF-23、RBP4水平明显升高,且血清Klotho蛋白、TWEAK、FGF-23、RBP4水平与肾功能及CKD分期相关。     

2型糖尿病患者肾小管功能测定及其相关因素分析

目的：探讨2型糖尿病（DM）患者的肾小管功能改变,分析其相关因素。方法：将64例2型DM患者根据尿微量白蛋白量分为3组：正常蛋白尿组（〈30mg/24h）21例、微量白蛋白尿组（30~300mg/24h）20例和临床蛋白尿组（〉300mg/24h）23例,测定各组尿β2微球蛋白（U-β2MG）和尿渗透压（U-OSM）。探讨年龄、DM病程、24h尿白蛋白量、糖化血红蛋白、血压、血脂水平与肾小管功能损害的关系。结果：2型DM患者均有不同程度的尿β2MG增高及尿渗透压减低,在正常蛋白尿组即有4例尿β2-MG和7例尿OSM存在异常;方差分析显示,随尿白蛋白量的增高,尿β2MG逐步增高,尿渗透压逐步减低,三组间差异有统计学意义（F=26.123和13.889,P均〈0.01）,任两组比较差异均有统计学意义（P均〈0.05）。线性回归显示,尿β2MG及尿OSM改变与DM病程、尿白蛋白（U-ALB）、收缩压（SBP）、糖化血红蛋白（HbA1c）、总胆固醇（TC）、低密度脂蛋白（LDL-C）独立有关。结论：2型DM肾脏损害并非仅累及肾小球,在尿微量白蛋白出现之前即可出现肾小管功能异常。联合检测24h尿白蛋白量、尿β2-MG、尿OSM有助于全面评估2型糖尿病患者的肾脏损害情况。严格控制血糖,尽早纠正代谢紊乱对肾小管功能有保护作用。     

2 型糖尿病患者肾小管功能测定及其相关因素分析

目的:探讨2型糖尿病(DM)患者的肾小管功能改变,分析其相关因素。方法:将64例2型DM患者根据尿微量白蛋白量分为3组:正常蛋白尿组(<30mg/24h)21例、微量白蛋白尿组(30~300mg/24h)20例和临床蛋白尿组(>300mg/24h)23例,测定各组尿β2微球蛋白(U-β2MG)和尿渗透压(U-OSM)。探讨年龄、DM病程、24h尿白蛋白量、糖化血红蛋白、血压、血脂水平与肾小管功能损害的关系。结果:2型DM患者均有不同程度的尿β2MG增高及尿渗透压减低,在正常蛋白尿组即有4例尿β2-MG和7例尿OSM存在异常;方差分析显示,随尿白蛋白量的增高,尿β2MG逐步增高,尿渗透压逐步减低,三组间差异有统计学意义(F=26.123和13.889,P均<0.01),任两组比较差异均有统计学意义(P均<0.05)。线性回归显示,尿β2MG及尿OSM改变与DM病程、尿白蛋白(U-ALB)、收缩压(SBP)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、低密度脂蛋白(LDL-C)独立有关。结论:2型DM肾脏损害并非仅累及肾小球,在尿微量白蛋白出现之前即可出现肾小管功能异常。联合检测24h尿白蛋白量、尿β2-MG、尿OSM有助于全面评估2型糖尿病患者的肾脏损害情况。严格控制血糖,尽早纠正代谢紊乱对肾小管功能有保护作用。     

前列地尔联合川芎嗪治疗早期糖尿病肾病的疗效观察

目的:观察前列地尔(凯时)联合川芎嗪注射液(川青)治疗糖尿病肾病的临床疗效,探讨其降低尿蛋白,减轻肾损害的机制.方法:收集早期2型糖尿病患者120例,随机分成川芎嗪组(40例)、前列地尔组(40例)和联合治疗组(40例).全部病例进行临床观察2周,分别比较三组血肌酐(Cr)、尿素氮(BUN)、24 h尿蛋白定量治疗前后的变化.结果:治疗2周后,联合治疗组降低24 h尿蛋白定量的作用优于川芎嗪组和前列地尔组差异有统计学意义(P＜0.05).前列地尔组和川芎嗪组比较,差异有统计学意义(P＜0.05).结论:静脉应用前列地尔联合川芎嗪注射液能够降低糖尿病肾病患者尿蛋白,延缓糖尿病肾病的进展,值得临床推广.     

高原寒环境暴露对急进入高原健康人群肾功能的影响

目的:探讨高原低压低氧寒环境对急进高原的平原健康人群肾功能的影响。方法:选取30例长期居住兰州地区急进高原(海拔3300米、日平均气温-4度)健康人群,对比分析所有受试者进驻高原前和进驻高原后第24 h、72 h、7天、14天、28天尿IL-18(白介素-18)、尿NAGL(中性粒细胞明胶酶相关性脂质运载蛋白)、尿KIM-1(肾损伤因子-1)及血肌酐水平的变化。结果:共28人完成全部6次尿液及血标本采集并检测,其中2名女性因某次采集点处于月经期剔除,其中男性17人、女性11人,平均年龄26.8±3.2岁(男性28.3±4.2岁,女性24.8±2.6岁)。进入高原前和进驻高原后第24 h、72 h、7天、14天、28天尿IL-18检测值分别为3.62±0.32 ng/L、11.20±0.65 ng/L(P<0.001,较进入前组比较)、6.32±0.46 ng/L(P<0.001)、4.36±0.68 ng/L(P<0.05)、3.58±0.71 ng/L、3.32±0.46 ng/L;尿NAGL水平分别为0.126±0.20μg/L、0.513±0.003μg/L(P<0.001)、0.116±0.006μg/L、0.009±0.001μg/L、0.121±0.010μg/L、0.632±0.009μg/L;尿KIM-1水平分别为2.61±0.22 ng/L、18.20±0.69 ng/L(P<0.001)、6.32±0.46 ng/L(P<0.001)、6.36±0.68 ng/L(P<0.001)、2.58±0.31 ng/L、2.32±0.26 ng/L;血肌酐水平分别为61.0±9.16μmol/L、58.5±8.13μmol/L、80.3±10.38μmol/L(P<0.05)、76.5±12.04μmol/L(P<0.05)、62.6±10.14μmol/l、62.3±8.18μmol/L。结论:急进高原健康入群早期肾功能有改变,其中尿IL-18、尿KIM-1、尿NAGL水平较血肌酐水平变化更早、更敏感。     

糖适平对2 型糖尿病合并糖尿病肾病4 期患者血糖、肌酐清除率及尿蛋白水平的影响

目的:探讨糖适平对2型糖尿病合并糖尿病肾病4期患者血糖、肌酐清除率及尿蛋白水平的影响。方法:选择我院收治的2型糖尿病合并糖尿病肾病4期患者100例,按照用药情况分为糖适平实验组和胰岛素对照组,每组50例。对照组患者给予预混人胰岛素及阿卡波糖片,实验组患者给予糖适平及阿卡波糖片。比较治疗前后两组患者空腹血糖(FBG)、肌酐清除率(CCr)、血清肌酐(SCr)、血尿素氮(BUN)及24小时尿蛋白定量(24 h Upro)水平的变化情况。结果:与治疗前相比,两组患者治疗后空腹血糖、血清肌酐、血尿素氮及24小时尿蛋白定量、肌酐清除率均明显改善,差异具有统计学意义(P0.05),但实验组与对照组比较差异无统计学意义(P0.05)。结论:糖适平对2型糖尿病合并糖尿病肾病4期患者无药物积蓄问题,用于治疗2型糖尿病合并糖尿病肾病4期安全有效。     

On the origin of the Hirudinea and the demise of the Oligochaeta

The phylogenetic relationships of the Clitellata were investigated with a data set of published and new complete 18S rRNA gene sequences of 51 species representing 41 families. Sequences were aligned on the basis of a secondary structure model and analysed with maximum parsimony and maximum likelihood. In contrast to the latter method, parsimony did not recover the monophyly of Clitellata. However, a close scrutiny of the data suggested a spurious attraction between some polychaetes and clitellates. As a rule, molecular trees are closely aligned with morphology-based phylogenies. Acanthobdellida and Euhirudinea were reconciled in their traditional Hirudinea clade and were included in the Oligochaeta with the Branchiobdellida via the Lumbriculidae as a possible link between the two assemblages. While the 18S gene yielded a meaningful historical signal for determining relationships within clitellates, the exact position of Hirudinea and Branchiobdellida within oligochaetes remained unresolved. The lack of phylogenetic signal is interpreted as evidence for a rapid radiation of these taxa. The placement of Clitellata within the Polychaeta remained unresolved. The biological reality of polytomies within annelids is suggested and supports the hypothesis of an extremely ancient radiation of polychaetes and emergence of clitellates.     

On the ontogeny of the haptor and the evolution of the Monogenea

Data on the ontogeny of the posterior haptor of monogeneans were obtained from more than 150 publications and summarised. These data were plotted into diagrams showing evolutionary capacity levels based on the theory of a progressive evolution of marginal hooks, anchors and other attachment components of the posterior haptor in the Monogenea (Malmberg, 1986). 5 + 5 unhinged marginal hooks are assumed to be the most primitive monogenean haptoral condition. Thus the diagrams were founded on a 5 + 5 unhinged marginal hook evolutionary capacity level, and the evolutionary capacity levels of anchors and other haptoral attachement components were arranged according to haptoral ontogenetical sequences. In the final plotting diagram data on hosts, type of spermatozoa, oncomiracidial ciliation, sensilla pattern and protonephridial systems were also included. In this way a number of correlations were revealed. Thus, for example, the number of 5 + 5 marginal hooks correlates with the most primitive monogenean type of spermatozoon and with few sensillae, many ciliated cells and a simple protonephridial system in the oncomiracidium. On the basis of the reviewed data it is concluded that the ancient monogeneans with 5 + 5 unhinged marginal hooks were divided into two main lines, one retaining unhinged marginal hooks and the other evolving hinged marginal hooks. Both main lines have recent representatives at different marginal hook evolutionary capacity levels, i.e. monogeneans retaining a haptor with only marginal hooks. For the main line with hinged marginal hooks the name Articulon-choinea n. subclass is proposed. Members with 8 + 8 hinged marginal hooks only are here called Proanchorea n. superord. Monogeneans with unhinged marginal hooks only are here called Ananchorea n. superord. and three new families are erected for its recent members: Anonchohapteridae n. fam., Acolpentronidae n. fam. and Anacanthoridae n. fam. (with 7 + 7, 8 + 8 and 9 + 9 unhinged marginal hooks, respectively). Except for the families of Articulonchoinea (e.g. Acanthocotylidae, Gyrodactylidae, Tetraonchoididae) Bychowsky's (1957) division of the Monogenea into the Oligonchoinea and Polyonchoinea fits the proposed scheme, i.e. monogeneans with unhinged marginal hooks form one old group, the Oligonchoinea, which have 5 + 5 unhinged marginal hooks, and the other group form the Polyonchoinea, which (with the exception of the Hexabothriidae) has a greater number (7 + 7, 8 + 8 or 9 + 9) of unhinged marginal hooks. It is proposed that both these names, Oligonchoinea (sensu mihi) and Polyonchoinea (sensu mihi), will be retained on one side and Articulonchoinea placed on the other side, which reflects the early monogenean evolution. Except for the members of Ananchorea [Polyonchoinea], all members of the Oligonchoinea and Polyonchoinea have anchors, which imply that they are further evolved, i.e. have passed the 5 + 5 marginal hook evolutionary capacity level (Malmberg, 1986). There are two main types of anchors in the Monogenea: haptoral anchors, with anlages appearing in the haptor, and peduncular anchors, with anlages in the peduncle. There are two types of haptoral anchors: peripheral haptoral anchors, ontogenetically the oldest, and central haptoral anchors. Peduncular anchors, in turn, are ontogenetically younger than peripheral haptoral anchors. There may be two pairs of peduncular anchors: medial peduncular anchors, ontogentically the oldest, and lateral peduncular anchors. Only peduncular (not haptoral) anchors have anchor bars. Monogeneans with haptoral anchors are here called Mediohaptanchorea n. superord. and Laterohaptanchorea n. superord. or haptanchoreans. All oligonchoineans and the oldest polyonchoineans are haptanchoreans. Certain members of Calceostomatidae [Polyonchoinea] are the only monogeneans with both (peripheral) haptoral and peduncular anchors (one pair). These monogeneans are here called Mixanchorea n. superord. Polyonchoineans with peduncular anchors and unhinged marginal hooks are here called the Pedunculanchorea n. superord. The most primitive pedunculanchoreans have only one pair of peduncular anchors with an anchor bar, while the most advanced have both medial and lateral peduncular anchors; each pair having an anchor bar. Certain families of the Articulonchoinea, the Anchorea n. superord., also have peduncular anchors (parallel evolution): only one family, the Sundanonchidae n. fam., has both medial and lateral peduncular anchors, each anchor pair with an anchor bar. Evolutionary lines from different monogenean evolutionary capacity levels are discussed and a new system of classification for the Monogenea is proposed.In agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. EditorIn agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. Editor