骨髓间充质干细胞联合维生素E对急性肾损伤炎症反应的抑制作用

 目的:探索骨髓间充质干细胞联合维生素E对急性肾损伤中炎症反应的抑制效果,开发针对急性肾损伤的新型治疗模式。方法:采用庆大霉素作为急性肾损伤药物,复制大鼠急性肾损伤模型,以骨髓间充质干细胞联合维生素E对急性肾损伤进行治疗,治疗结束后,收集大鼠的血浆和肾脏组织,采用实时荧光定量PCR及ELISA方法,评价血浆及组织中炎症蛋白的表达。结果:通过骨髓间充质干细胞联合维生素E对大鼠急性肾损伤模型进行治疗后,大鼠血浆中的炎症蛋白显著降低;在肾脏组织中,与单一应用骨髓间充质干细胞或维生素E相比,二者联合在某些炎症蛋白的抑制方面具有更明显的效果。结论: 骨髓间充质干细胞联合维生素E对急性肾损伤中炎症反应具有一定抑制效果,优于单一骨髓间充质干细胞或单一维生素E的治疗方式,所以,这种联合治疗模式在急性肾损伤的治疗方面更具有临床应用价值。     

心脏脱细胞支架的制备及其生物相容性

目的:优化心脏脱细胞支架的制备方法,评价所制备的脱细胞支架的基本生物学特征。方法:联合应用十二烷基硫酸钠(SDS)和聚乙二醇辛基苯基醚(Triton X-100)对大鼠心行逆行主动脉灌流制备心脏脱细胞支架。同时,将间充质干细胞(MSCs)接种到支架上构建细胞支架复合体,采用H-E染色及扫描电镜分别对制备支架及复合体进行评价。结果:心脏脱细胞支架大体呈半透明囊状。组织学染色及扫描电镜观察示支架呈多孔网状或束状结构,未见细胞核残留。荧光显微镜观察示MSCs沿支架纤维黏附生长,未见明显坏死细胞。结论:本研究运用灌流法成功制备脱细胞彻底且细胞外基质保留较完整的心脏脱细胞支架,既拥有天然三维结构且具有良好的生物相容性。     

间充质干细胞对脊髓损伤治疗的研究进展

文题释义：脊髓损伤：由于外界直接或间接因素导致的脊髓相应节段损伤,损伤后出现各种运动、感觉和括约肌功能障碍、肌张力异常及病理反射等相应改变。如何使受损的神经结构进行再生和修复,从而促进神经功能的恢复仍是当前治疗的难点和研究的热点。脊髓损伤主要表现在急性期出现脊髓损伤处神经元的坏死、少突胶质细胞的凋亡、髓鞘的崩解、神经束变性坏死以引发的炎症反应等。对于脊髓损伤的治疗往往是通过对以上几方面的修复来实现的。 间充质干细胞移植治疗脊髓损伤的作用机制：间充质干细胞以其高度的可塑性、在一定条件下可向神经细胞诱导分化等优点使其可以在不同个体间移植。间充质干细胞体内移植后通过分化为神经细胞替代已损伤的神经元;间充质干细胞进入病变区后通过旁分泌释放大量的抗炎因子、细胞因子、生长因子及细胞黏附因子来改变脊髓损伤微环境;间充质干细胞能产生多种细胞外基质,促进神经元轴突再生、髓鞘化并可诱导细胞方向性生长和迁移等。   摘要背景：脊髓损伤是人类致残率最高的疾病之一,由于脊髓轴突再生能力有限,恢复难度大,常导致严重的神经后遗症,对脊髓损伤治疗方法的探索已成为研究热点。随着生物学及分子生物学研究的不断深入,研究发现间充质干细胞治疗脊髓损伤表现出巨大的潜力,为脊髓损伤的修复带来了曙光。 目的：综述间充质干细胞对于脊髓损伤的治疗作用、性质、应用、局限性及发展前景。 方法：检索PubMed、Web of Science数据库及万方、CNKI中国期刊全文数据库收录的间充质干细胞治疗脊髓损伤的相关文章,英文检索词为“spinal cord injury,mesenchymal stem cell”,中文检索词为“脊髓损伤,间充质干细胞”,按纳入和排除标准共纳入文献85篇进行归纳总结。结果与结论：间充质干细胞通过多种作用机制修复脊髓损伤,如间充质干细胞体内移植后通过分化为神经细胞替代已损伤的神经元;通过旁分泌机制分泌各种营养物质来改变脊髓损伤微环境的变化;同时间充质干细胞产生多种细胞外基质,为再生轴突提供支持物,促进神经元轴突再生。虽然在基础实验中间充质干细胞治疗脊髓损伤能起到较好的疗效,但间充质干细胞在临床中的应用却差强人意,还需要更深入地探索间充质干细胞对于脊髓损伤的作用机制。 ORCID: 0000-0002-3216-3301(史旭) 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

脱细胞胶原基质双层材料与骨髓间充质干细胞的生物相容性研究

目的 对脱细胞胶原基质双层材料和骨髓间充质干细胞（BMSCs）间的生物相容性进行研究.方法 将BMSCs与脱细胞胶原基质双层材料共培养作为实验组,单独培养的BMSCs为对照组,对BMSCs的生长和增殖情况进行研究,扫描电镜下观察细胞在材料上的贴附生长情况,并采用CCK-8法测定细胞活性.结果 扫描电镜结果显示BMSCs在脱细胞胶原基质双层材料上生长良好.CCK-8法测得的BMSCs与脱细胞胶原基质双层材料共培养的生长曲线显示,实验组与对照组间差异无统计学意义（P＞0.05）.结论 脱细胞胶原基质双层材料具有较好的生物相容性,这为脱细胞胶原基质组织工程支架双层材料下阶段在体内动物中的应用提供了科学依据.     

急性肾损伤相关生物标志物的研究进展

急性肾损伤(acute kidney injury,AKI)既往被称为急性肾衰竭(acute renal failure,ARF),是一种由不同病因所致、具有不同临床表现并以肾小球滤过率迅速下降为主要特点的临床综合征,多见于多器官功能衰竭、败血症等严重疾病,也常见于各类肾脏疾病的不同阶段.     

基因多态性与急性肾损伤的研究进展

正急性肾损伤(acute kidney injury,AKI)表现为多种原因造成的肾功能急性下降,是影响多器官、多系统的临床重症。尽管近年来重症监护病房(intensive care unit,ICU)治疗及肾脏替代技术均有了长足的进步,但死亡率却无明显下降。早期诊断和治疗对减少患者的并发症,降低死亡率有着重要意义。2005年国际肾脏病学界和急救医学界提出应用"急性肾损伤"来取代传统"急性肾功能衰竭"的概念,目的是     

Clinical features and outcomes of acute kidney injury among patients with acute hepatitis A

Background

Although acute hepatitis A is usually self-limited, the clinical manifestations can vary from mild to severe liver dysfunction. However, little is known about risk factors for and outcomes of acute kidney injury (AKI) in acute hepatitis A.

Objectives

To identify the risk factors for and outcomes of AKI in acute hepatitis A.

Study design

We identified 396 patients with acute hepatitis A, which registered between January 2006 and June 2009 at a tertiary care university hospital. Retrospective case-control studies were conducted in order to identify risk factors for AKI.

Results

Thirty patients (7.6%) developed AKI. On multivariate analysis, fulminant hepatitis, leukocytosis, and elevated CRP were independent risk factors for AKI associated with hepatitis A, and higher total bilirubin, leukocytosis, and elevated CRP were independent risk factor for AKI within nonfulminant hepatitis A. Of the 30 patients with AKI, 23 (76.7%) patients fully recovered, 2 patients maintained hemodialysis after hospital discharge and 5 patients died due to hepatic failure without recovery from AKI. Among 20 patients with AKI in nonfulminant subgroup, 19 patients (95%) recovered without hemodialysis.

Conclusions

AKI is not a rare complication of acute hepatitis A and severity of hepatitis and hepatic injury influence the development of AKI in acute hepatitis A.     

Impact of acute kidney injury on clinical outcomes after ST elevation acute myocardial infarction

Purpose

This study aimed to compare the incidence and clinical significance of transient versus persistent acute kidney injury (AKI) on acute ST elevation myocardial infarction (STEMI).

Materials and Methods

The study was a retrospective cohort of 855 patients with STEMI. AKI was defined as an increase of ≥0.3 mg/dL in creatinine level at any point during hospital stay. The study population was classified into 5 groups: 1) patients without AKI; 2) patients with mild AKI that was resolved by discharge (creatinine change less than 0.5mg/dL compared with admission creatinine during hospital stay, transient mild AKI); 3) patients with mild AKI that did not resolve by discharge (persistent mild AKI); 4) patients with moderate/severe AKI that was resolved by discharge (creatinine change more than 0.5 mg/dL compared with admission creatinine, transient moderate/severe AKI); 5) patients with moderate/severe AKI that did not resolve by discharge (persistent moderate/severe AKI). We investigated 1-year all-cause mortality after hospital discharge for the primary outcome of the study. The relation between AKI and 1-year mortality after STEMI was analyzed.

Results

AKI occurred in 74 (8.7%) patients during hospital stay. Adjusted hazard ratio for mortality was 3.139 (95% CI 0.764 to 12.897, p=0.113) in patients with transient, mild AKI, and 8.885 (95% CI 2.710 to 29.128, p<0.001) in patients with transient, moderate/severe AKI compared to patients without AKI. Persistent moderate/severe AKI was also independent predictor of 1 year mortality (hazard ratio, 5.885; 95% CI 1.079 to 32.101, p=0.041).

Conclusion

Transient and persistent moderate/severe AKI during acute myocardial infarction is strongly related to 1-year all cause mortality after STEMI.     

Nestin+ kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury

Renal resident mesenchymal stem cells (MSCs) are important regulators of kidney homeostasis, repair or regeneration. However, natural distribution and the starting population properties of these cells remain elusive because of the lack of specific markers. Here, we identified post-natal kidney derived Nestin⁺ cells that fulfilled all of the criteria as a mesenchymal stem cell. These isolated Nestin⁺ cells expressed the typical cell-surface marker of MSC, including Sca-1, CD44, CD106, NG2 and PDGFR-α. They were capable of self-renewal, possessed high clonogenic potential and extensive proliferation for more than 30 passages. Under appropriate differentiation conditions, these cells could differentiate into adipocytes, osteocytes, chondrocytes and podocytes. After intravenous injection into acute kidney injury mice, Nestin⁺ cells contributed to functional improvement by significantly decreasing the peak level of serum creatinine and BUN, and reducing the damaged cell apoptosis. Furthermore, conditioned medium from Nestin⁺ cells could protect against ischemic acute renal failure partially through paracrine factor VEGF. Taken together, our findings indicate that renal resident Nestin⁺ MSCs can be derived, propagated, differentiated, and repair the acute kidney injury, which may shed new light on understanding MSCs biology and developing cell replacement therapies for kidney disease.     

65例老年慢性肾脏病基础上急性肾损伤的临床观察

目的 分析老年慢性肾脏病基础上急性肾损伤(A/C)的基础疾病、发病诱因及影响预后的危险因素.方法 回顾性分析2005年12月至2009年12月于本院住院治疗的65例老年A/C患者的临床资料,分析A/C患者的基础疾病、发病诱因及影响预后的危险因素.根据治疗后肾功能恢复情况将患者分为2组:肾功能恢复患者和肾功能部分恢复患者合并为肾功能恢复组,肾功能未恢复患者与死亡患者合并为肾功能未恢复组,比较两组患者的少尿持续时间、入院时血清白蛋白水平和最高血清肌酐(Scr)水平.结果 糖尿病肾病是老年A/C患者的主要基础疾病(38.5％,25/65),药物因素(30.8％,20/65)和严重感染(27.7％,l8/65)是老年A/C患者的主要发病诱因.与肾功能恢复组比较,肾功能未恢复组患者少尿持续时间较长[(1 1.5±3.4)d比(4.2±1.8)d,P＜0.05]、入院时血清白蛋白水平较低[(23.6±3.1)g/L比(26.6± 4.5) g/L,P＜0.05],而最高Scr水平较高[(601.2± 142.7) μmol/L比(421.3±107.3) μmol/L,P＜0.05].结论 老年A/C患者应对其基础疾病进行有效治疗,积极消除发痫诱因和控制影响预后的危险因素.     

Iron,ferroptosis, and new insights for prevention in acute kidney injury

Acute kidney injury (AKI) is a very common condition with high morbidity and mortality, which can be seen in 5–7% of all hospitalized patients and in up to 57% of all intensive care unit admissions. Despite recent advances in clinical care, the prevalence of AKI has been shown to increase with virtually no change in mortality. AKI is a complex syndrome occurring in a variety of clinical settings. Early detection is crucial to prevent irreversible loss of renal function. The pathogenesis of AKI is highly multifactorial and complex, including vasoconstriction, reactive oxygen species formation, cell death, abnormal immune modulators and growth factors. Emerging evidence from both human and animal studies suggests that dysregulation of iron metabolism may play a potentially important role in AKI. Therefore, targeting the iron homeostasis may provide a new therapeutic intervention for AKI. New therapeutic strategies including iron chelation therapy, targeting iron metabolism related proteins and direct inhibitors of ferroptosis are imperative to improve the outcomes of patients. Taking into consideration the complexity of AKI, one intervention may not be enough for therapeutic success. Future preclinical studies in animal disease models followed by well-designed clinical trials should be conducted to extend findings from animal AKI models to humans.     

Diagnostic value of cystatin C for predicting acute kidney injury in patients with liver cirrhosis

Background/Aims

The present study aimed to determine the role of cystatin C as a prognostic factor for acute kidney injury and survival in cirrhotic patients.

Methods

The study investigated 53 liver cirrhosis patients. The renal function was evaluated by serum creatinine, serum and urine cystatin C, and 24-hour creatinine clearance on admission. Acute kidney injury was defined as a serum creatinine level exceeding the normal range (>1.2 mg/dl) and an increase of at least 50% from the baseline value. Multivariate analysis, receiver operating characteristic curve, and survival analysis were used to investigate prognostic factors for acute kidney injury and survival.

Results

Nine of the 53 cirrhotic patients (17.0%) developed acute kidney injury within 3 months. Both serum creatinine and cystatin C were predictive factors for acute kidney injury in univariate analysis, with a diagnostic accuracy of 0.735 (95% confidence interval (CI), 0.525-0.945; p=0.028) for serum cystatin C and 0.698 (95% CI, 0.495-0.901, p=0.063) for creatinine. In multivariate analysis, only serum cystatin C was an independent risk factor for acute kidney injury. The sensitivity and specificity of a serum cystatin C level of >1.23 mg/L to acute kidney injury were 66% and 86%, respectively. Serum cystatin C was positively correlated with the Model for End-Stage Liver Disease (MELD) and MELD-Na scores (r=0.346 and p=0.011, and r=0.427 and p=0.001, respectively). Comparison of the survival rates over the observation period revealed that a serum cystatin C level of >1.23 mg/L was a useful marker for short-term mortality (p<0.001).

Conclusions

The accuracy in predicting acute kidney injury and short-term mortality was higher for a serum cystatin C level of >1.23 mg/L than for the serum creatinine concentration in patients with cirrhosis.     

Transplantation of bone marrow-derived MSCs improves cisplatinum-induced renal injury through paracrine mechanisms

Mesenchymal stem cells (MSCs) have been reported to preserve renal function in various models of acute kidney injury (AKI). Different routes were used to transplant MSCs but the role of cell transplantation routes in directing outcomes has been unknown. In the present study, we evaluated organ bio-distributions of transplanted MSCs, and correlated survival of transplanted cells with outcomes in mice with cisplatinum-induced AKI. We found that after intravenous administration, MSCs were largely localized in pulmonary capillaries and only a minute fraction of MSCs entered kidneys and the cells survived only transiently. Therefore, we also transplanted MSCs via intraperitoneal and renal subcapsular routes. Transplanted MSCs survived longer in peritoneal cavity and renal subcapsular space. Interestingly, when MSC transplantation was followed by cisplatinum-induced AKI, renal morphology and renal functions were better preserved, irrespective of the cell transplantation route. As transplanted MSCs did not migrate to kidneys from either peritoneal cavity or renal subcapsular space, this finding suggested that migration of cells was not required for the beneficial response. The possibility of indirect mechanisms was confirmed when administration of the conditioned medium from MSCs also protected renal tubular cells from cisplatinum-induced cytotoxicity. We identified presence of over forty regulatory cytokines in the conditioned medium obtained from MSCs. Since paracrine factors released by transplanted cells accounted for improvements, it appears that the route of cell transplantation is not critical for realizing benefits of cell therapy with MSCs in AKI. Studies of specific cytokines secreted by MSCs will help to obtain new therapeutic mechanisms for renal protection.     

非黏附骨髓源干细胞治疗急性放射损伤

背景：目前对于辐射剂量超过8 Gy的急性放射病尚缺乏有效的治疗方案,间充质干细胞可以分泌多种造血因子、重建造血,在放射损伤救治中具有重要意义。 目的：探讨非黏附骨髓源干细胞在8.5 Gy X射线照射所致急性骨髓型放射损伤救治中的作用及作用机制。 方法：取胎儿四肢长骨的非黏附骨髓源干细胞,分析其麦面抗原,细胞周期,成骨和成脂分化潜能,以及血管内皮生长因子及Annexin A2表达。BALB/C小鼠受8.5 Gy一次性全身均匀X射线照射后随机分成骨髓源干细胞组和对照组,骨髓源干细胞组小鼠在X射线照射2 h内经尾静脉输注含3×106 CFDA-SE标记的人非黏附骨髓源干细胞的细胞悬液0.3 mL,对照组小鼠在X射线照射2 h内输注0.3 mL生理盐水。观察骨髓源干细胞的分布情况、小鼠的存活率、白细胞变化、骨髓病理变化及骨髓中新生血管形成情况。 结果与结论：X射线照射后移植的非黏附间充质干细胞可以向损伤部位归巢;骨髓源干细胞组小鼠存活率明显高于对照组;与对照组相比,骨髓源干细胞组小鼠外周血白细胞计数下降慢且恢复迅速,X射线照射后14 d左右达最低,30 d基本恢复至正常水平。X射线照射后21 d,骨髓源干细胞组骨髓增生活跃,骨髓腔内新生造血灶显著多于对照,血管密度亦显著高于对照组。说明人胎儿非黏附骨髓源干细胞促进急性放射损伤小鼠骨髓内新生血管形成,改善并加快受损小鼠造血功能的恢复。     

Mesenchymal stem cell-based angiopoietin-1 gene therapy for acute lung injury induced by lipopolysaccharide in mice

Bone marrow-derived mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. Angiopoietin-1 (Ang1) is a critical factor for endothelial survival and vascular stabilization via the inhibition of endothelial permeability and leukocyte-endothelium interactions. We hypothesized that MSC-based Ang1 gene therapy might be a potential therapeutic approach for lipopolysaccharide (LPS)-induced lung injury. MSCs were isolated from 6 week-old inbred male mice and transduced with the Ang1 gene, using a lentivirus vector. The MSCs showed no significant phenotypic changes after transduction. In the in vivo mouse model, the LPS-induced lung injury was markedly alleviated in the group treated with MSCs carrying Ang1 (MSCs-Ang1), compared with groups treated with MSCs or Ang1 alone. The expression of Ang1 protein in the recipient lungs was increased after MSCs-Ang1 administration. The histopathological and biochemical indices of LPS-induced lung injury were improved after MSCs-based Ang1 gene treatment. MSCs-Ang1 administration also reduced pulmonary vascular endothelial permeability and the recruitment of inflammatory cells into the lung. Cells of MSC origin could be detected in the recipient lungs for 2 weeks after injection with MSCs. These results suggest that MSCs and Ang1 have a synergistic role in the treatment of LPS-induced lung injury. MSC-based Ang1 gene therapy may be developed as a potential novel strategy for the treatment of acute lung injury.     

大鼠急性肾损伤导致肝细胞凋亡的实验研究

 目的：观察大鼠急性肾损伤（AKI）引起肝细胞凋亡的细胞学特点。方法：建立AKI（包括缺血性和非缺血性）大鼠模型后应用免疫印迹法、免疫组织化学染色法和光学、电子显微镜技术对AKI大鼠的肾脏和肝脏进行观察。结果：(1) 缺血性AKI 肾小管出现了大面积细胞坏死和细胞凋亡的表现。不论是缺血性还是非缺血性AKI的动物都发生了急性肾功能损伤和急性肝功能受损。(2) 免疫印迹法测定结果显示AKI动物肝脏的肿瘤坏死因子受体α（TNFRα）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）蛋白表达增强。从caspase-3免疫组化染色的结果可以看出阳性细胞均出现在AKI动物肝脏内。(3) 电子显微镜观察发现AKI动物肝脏中确有细胞凋亡和副凋亡的表现。(4) 缺血性与非缺血性AKI诱导肝细胞凋亡的表现相同。结论：AKI可引起肝细胞凋亡和副凋亡,其中经TNFRα启动的caspase依赖的细胞死亡构成了AKI引起的肝细胞凋亡。这种肝细胞凋亡是由肾功能损伤导致的血尿毒物质引起的。     

骨髓间充质干细胞移植促进大鼠肾缺血再灌注损伤的恢复

目的 观察骨髓间充质干细胞(MSCs) 缺血再灌注肾损伤大鼠体内的分化情况及对肾修复的促进作用.方法 72只雌性6周龄sD大鼠随机分为正常组、假手术组、缺血再灌注(I/R)组、MSCs移植组4组,分别于再灌注后12 h、3、7、14、42 d随机选取I/R组和MSCs组大鼠各6只,收获肾脏标本和血标本.测定血标本尿素氮和肌酐值;肾脏切片行HE染色、免疫组化PCNA染色、TUNEL法检测原位凋亡、激光共聚焦显微镜观察MSCs分化情况.结果 再灌注后7 d内,与I/R组比较,MSCs组BUN值、Scr值明显降低(P<0.05),组织学评分明显减低,PCNA阳性细胞数明显增多(P<0.05).再灌注后12 h,MSCs组凋亡细胞数少于I/R组(P<0.05).再灌注后42 d,肾小管中有BrdU阳性细胞.结论 MSCs移植可减轻急性肾缺血再灌注损伤鼠肾小管上皮细胞的损伤,促进肾功能恢复.少部分MSCs在体内可分化形成肾小管上皮细胞.     

MSCs-FGF2基因治疗对急性肺损伤小鼠的保护作用

目的研究间充质干细胞-纤维母细胞生长因子2(MSCsFGF2)基因治疗对脂多糖诱导的急性肺损伤小鼠的保护作用。方法 40只雄性C57/B6小鼠随机分为对照组、急性肺损伤组、MSCs组、MSCs-FGF2组,每组10只。应用脂多糖建立小鼠急性肺损伤模型,观察4组小鼠肺组织病理改变、计算肺损伤评分、计算肺组织湿重与干重比值,计数支气管肺泡灌洗液(BALF)中中性粒细胞数量,实时PCR方法检测小鼠肺组织FGF2 mRNA表达,Western印迹法测定小鼠肺组织FGF2蛋白表达,ELISA法测定小鼠BALF中TNF-α和IL-6浓度。结果与急性肺损伤组小鼠比较,MSCs-FGF2组小鼠肺组织病理改变明显减轻、肺损伤评分明显降低(P0.05)、肺组织湿重与干重比值明显降低(P0.05)、BALF中中性粒细胞数量明显降低(P0.05)、肺组织FGF2 mR NA及蛋白表达量明显增加(P0.05)、BALF中TNF-α和IL-6浓度明显降低(P均0.05)。结论 MSCs-FGF2基因治疗对脂多糖诱导的急性肺损伤小鼠有确切的保护作用。     

hUCMSCs腹腔移植治疗大鼠急性肝损伤后的病理变化

目的本研究拟对CCl所致大鼠急性肝损伤模型应用人脐带间充质干细胞(humanum bilical cord mesenchymal stem cells,hUCMSCs)进行治疗,观察其效果。方法将健康雌性150-170gSD大鼠随机分为3组:正常对照组(N,n=8),CCl_4组(C,n=32)及CCl_4+MSCs组(T,n=32)。N组不予任何处理;T组和C组腹腔注射10%(V/V)四氯化碳(carbon tetrachloride,CCl_4)橄榄油溶液制造急性肝损伤模型后24h,分别经腹腔移植hUCMSCs和等量PBS。肝功能测定、病理组织学方法观察移植前后大鼠肝功能及肝脏结构改善情况。结果 CCl腹腔注射24h后大鼠肝脏的HE染色示弥漫性肝小叶中心带肝细胞气球样变或脂肪变性,可见炎性细胞浸润。4随着观察时间的推移,上述组织学变化均好转,T组较C组更早更快的恢复,7d时肝脏结构完全恢复正常,C组7d时仍可见脂滴或气球样变,14d才恢复正常肝脏组织结构。MSCs移植后3d,T组与C组比较,肝损伤大鼠的ALT(p<0.05)及AST(p<0.01)水平明显降低,说明MSCs移植可降低CCl_4所致大鼠肝脏损伤的ALT及AST水平。47d后,所有观察组的ALT及AST均降至正常水平。结论鼠腹腔移植hUCMSCs后可以在一定程度上改善肝功能及修复受损的肝组织。     

叉头框蛋白O1在内毒素血症急性肾损伤中的作用

目的:探讨叉头框蛋白O1(forkhead box protein O1,FOXO1)在内毒素血症急性肾损伤(acute kidney injury,AKI)中的作用及相关机制。方法:6～8周龄雄性C57BL/6小鼠腹腔内注射脂多糖(lipopolysaccharide,LPS; 10 mg/kg)诱导内毒素血症AKI模型,检测血清肌酐和血尿素氮。利用Western blot、RT-qPCR和免疫荧光等方法检测小鼠肾组织内FOXO1的表达变化。体外培养人近端肾小管上皮细胞HK-2,LPS诱导内毒素血症AKI肾小管上皮细胞模型,利用FOXO1过表达腺病毒感染HK-2细胞,MTT法检测细胞活力;MitoTracker标记线粒体形态学变化;Mito-SOX检测线粒体超氧化物含量改变;检测FOXO1、促凋亡因子Bax及线粒体氧化磷酸化相关分子mRNA变化,以观察线粒体氧化损伤变化情况。结果:内毒素血症AKI小鼠肾组织FOXO1 mRNA及蛋白表达下调。体外LPS刺激可引起HK-2细胞活力下降,线粒体片段化改变,线粒体超氧化物含量升高,FOXO1 mRNA及蛋白表达下调,Bax表达上调,线粒体氧...