对矽肺发病概况及机制、矽肺治疗现状做了回顾,对干细胞治疗在矽肺中的应用做了分析和展望.认为,鉴于缺乏有效的治疗干预措施,干细胞疗法成为矽肺治疗中一个有前途的方法.干细胞是一类能够自我复制的多潜能细胞,具有较强分化功能,由于干细胞的潜能区分,它可替换目标组织中的受损细胞.这种疗法的关键作用包括减少有害的促炎症和促纤维化过程,减少细胞凋亡,以及增强肺损伤后的修复.细胞治疗方案的优化和临床试验的进步可以带来矽肺治疗的重要突破.
Inflammation is implicated in the pathogenesis of diabetic nephropathy (DN). Toll-like receptor 2 (TLR2) is a ligand-activated membrane-bound receptor, which induces an inflammatory response, thus serving a crucial role in the pathogenesis of DN. The present study aimed to determine whether a TLR2 agonist, Pam3CysSK4, modulates the development of DN. A mouse model of DN was induced using streptozotocin (STZ) and, following the confirmation of hyperglycemia, mice were treated with or without Pam3CysSK4. Pathological and functional markers, including the activation of nuclear factor (NF)-κB, expression of TLR2, inflammatory infiltration, myeloid differentiation primary response gene 88 and monocyte chemoattractant protein-1 were assessed. STZ-treated mice exhibited elevated blood glucose levels and increased serum creatinine levels, which increased further following Pam3CysSK4 treatment. In addition, Pam3CysSK4 treatment was observed to increase podocyte foot process formation. Furthermore, STZ-induced renal glomerular sclerosis was significantly exacerbated in Pam3CysSK4-treated mice. Pam3CysSK4-treated mice also exhibited increased levels of collagen IV following renal immunostaining, associated with increased macrophage infiltration. Renal expression of TLR2 was markedly elevated in STZ-induced mice; this was further increased in Pam3CysSK4-treated mice, accompanied by upregulation of proinflammatory genes and activation of NF-κB. This indicates that enhanced renal expression of TLR2 is associated with inflammatory infiltration in DN and demonstrates that renal injury was exacerbated by the TLR2 agonist in diabetic mice.
[目的]观察职业性镉作业观察对象尿镉及肾小管损伤效应标志物水平的变化,比较脱离镉作业6年后镉作业观察对象尿肾小管损伤分子-1(KIM-1)的水平.[方法]选取8例职业性镉作业观察对象,对2009-2014年度的尿镉、尿β2-微球蛋白及尿维生素A结合蛋白(即视黄醇结合蛋白)水平进行跟踪观察.2014年用ELISA法检测观察对象及正常对照组尿肾小管损伤分子-1(KIM-1)的水平.[结果]停止镉作业后,观察组的尿镉平均水平略有下降趋势,但各年度间差异无统计学意义(P>0.05).停止镉接触后,观察组尿β2-MG水平和尿视黄醇结合蛋白水平一直维持在正常范围.观察组各年度尿β2-MG水平、尿视黄醇结合蛋白水平差异均无统计学意义(P>0.05).停止镉接触6年后,观察组尿KIM-1的水平(1.37±0.61) ng/mL,对照组为(0.62±0.35)ng/mL,两组差异有统计学意义(P<0.05).[结论]镉作业观察对象脱离镉接触后,尿镉水平下降不明显,传统的肾小管功能损害标志物尿β2-MG及尿视黄醇结合蛋白水平无明显变化,但尿KIM-1仍存在异常.
Objective To investigate the effect of cadmium chloride on the expression of kidney injury molecule-1 ( KIM-1) in human renal tubular epithelial cells ( HK-2 cells ) .Methods HK-2 cells at logarithmic phase were divided into a control group and 5 treatment groups that were treated with 5.0, 10.0, 20.0, 50.0 and 100.0 μmol/L of cadmium chloride dissolved in phosphate buffer solution.Cell pathology observation was carried out after 24 hours of cultivation.The methyl thiazolyl tetrazolium assay was used to calculate the survival rate of HK-2 cells.The expression of KIM-1 mRNA and protein were detected by the reverse transcription-polymerase chain reaction and Western blotting analysis respectively. Results There were no cellular morphologic change in HK-2 cells in the control group, the 5.0 and 10.0μmol/L groups;the HK-2 cells showed different degree of swellings or vacuoles in the 20.0 and 50.0 μmol/L groups; a large number of cells were found dead in the 100.0 μmol/L group.The cell survival rates of HK-2 cells in the 20.0, 50.0 and 100.0μmol/L groups were lower than those of control group, the 5.0 and 10.0 μmol/L groups ( P <0.05 ) .The pairwise comparison among survival rates of the 20.0, 50.0 and 100.0 μmol/L groups showed significant difference (P<0.05). The expression levels of KIM-1 mRNA and protein in the 20.0 and 50.0 μmol/L groups were higher than those of control group, the 5.0 and 10.0 μmol/L groups (P<0.05).The levels of KIM-1 mRNA and protein in the 50.0 μmol/L group were higher than those of the 20.0 μmol/L group ( P<0.05 ) .Conclusion Cadmium chloride at certain concentration can increase the expression of KIM-1 mRNA and protein in HK-2 cells.Therefore, the expression of KIM-1 could be used as one of the effect biomarkers for cadmium induced kidney tubule injury.
Objective]To study the influence of Pam3CysSK4 on renal function of diabetic mice and TLR2 expres‐sion of the renal tubular epithelial cells .[Methods]Twenty‐four C57 mice were selected and randomly divided into the normal group ,diabetic model group (the model group) and the intervention group ,8 rats in each group .The model group was induced by the use of streptozotocin (STZ) to establish diabetes model in mice .The diabetic mice model was estab‐lished in the intervention group with intravenous injection of Pam3CysSK4 ,100 μg/ week ,The normal group mice was given with the same amounts of citrate buffer injection as the other two groups did .After they were fed for 8 weeks ,24 h urine and 24 h urine protein were collected and evaluated ,mice body and kidney were weighed and calculated ,and ser‐um creatinine (Cr) ,urea nitrogen (BUN) ,blood glucose and interleukin ‐1 (IL‐1) were detected to assess glomerular sclerosis index ,and detection was also made on Toll like receptors(TLR2) ,Nuclear Translocation factor κB (NF‐κB) , myeloiddifferentiationfactor88(MyD88) and monocyte chemotactic protein 1(MCP‐1) to find out their expression levels .[Results]The blood glucose levels of the intervention group and the model group were higher than that of the normal group .In the intervention group ,the kidney weight and kidney weight / body weight were higher than that of the model group ,while the model group was higher than the normal group ,the difference was statistically significant ( P < 0 .05) . Of the intervention group and model group ,the Cr ,bun ,IL‐1 and 24 h urinary protein content and glomerular sclerosis index ,TLR2 ,NF‐κB ,MyD88 and MCP‐1 were higher than those in normal control group ,the intervention group were significantly higher than the model group ,the differences were statistically significant ( P < 0 .05) .[Conclusion]High glu‐cose can increase TLR2 level of mouse renal tubular epithelial cells ,activate TLR signaling pathway ,promote the release of inflammatory factors and increase the damage to the kidney .
Objective To explore the influence on expression of KIM - 1 mRNA in HK - 2 cells induced by cadmium chloride. Methods Human renal proximal tubular epithelial cell line HK - 2 cells were cultured in DMEM medium supplemented with 10% FBS. Experiments were conducted in FBS - free medium containing various concentrations of cadmium chloride(10 μmol/ L,20 μmol/ L,40 μmol/ L and 80 μmol/ L). Morphological features and survival rates were detected after incubation for 24 hours. RT - PCR had been applied for measuring the expression of KIM - 1 mRNA. Results Cadmium chloride can injure the morphological features and decrease the viability of cells. The expression of KIM - 1 mRNA was significantly increased in HK - 2 cells in concentrations of cadmium chloride at 20 μmol/ L and 40 μmol/ L. Conclusion Cadmium chloride can induce the expression of KIM - 1 in HK - 2 cells,this indicates that KIM - 1 may be used as an effective marker for renal tubular im-pairment induced by cadmium chloride.
Objective To investigate effects of the Toll - liKe receptor 2 agonist on diabetic Kidney damage. Methods Diabetes was in-duced by intraperitoneal injection of streptozotocin. Diabetes mice were divided into diabetes control group(DM group)and Toll liKe receptor 2 ex-citomotor intervention group(intervention group). Immunohistochemistry was used for macrophage staining. The blood urea nitrogen,serum creati-nine,urinary albumin excretion and renal macrophage accumulation were compared between two group. Results There was more significant in-crease in blood urea nitrogen,serum creatinine level and macrophage infiltration in the Kidney of intervention group than those of DM group. Urina-ry albumin excretion increased significantly in the intervention group. Pathological study found that:the glomerular volume increased glomerular cysts shrinK,mesangial widening,basement membrane thicKening,and renal tubular hypertrophy in the DM group. In the intervention group, these changes were more significant. Conclusion Toll - liKe receptor 2 agonist in diabetic mice increased proteinuria,glomerular sclerosis,tubu-lar injury,inflammatory cell infiltration,confirmed that TLR2 agonist aggravated renal injury in diabetic mice.
Objective To explore the effect of cadmium chloride on the morphology of human renal tubular epithelial cell ( HK2-cell) and survival rate.Methods The HK-2 cells cultured with DMEM medium were randomly divided into six groups when they reached 70%to80%fusion.Groups A,B,C,D,E were given 5,10,20,50,100μmol/L of cadmium chlorine,respectively,with two parallel cell bottles in each group,and the culture lasted for 24 hours.Group F( control group) wasn′t given cadmium chlorine.The changes in cellular morphology were observed after 24 hours of incubation.Methyl thiazol tetrazolium( MTT) assay was used to detect the optical density( OD) value in each group,and the survival rates of the cells were calculated.Results The morphology of HK-2 cells showed no significant difference among control group,group A and group B.The HK-2 cells appeared morphological changes in group C ,with the decreasedcell viability.The survival rates of HK-2 cells in groups C,D,E were significantly lower than that in the control group (P<0.01).The survival rates of HK-2 cells in groups A, B showed no statistically difference compared with control group(P>0.05).Conclusion Cadmium chloride with the concentration of 20μmol/L or more might lead to HK-2 cell injury,damages to cellular morphology and decreased cell viability.
选取本院收治的80例早期糖尿病肾病(DN)患者临床资料,随机分为观察组与对照组,各40例。对照组接受常规治疗,观察组实施复方α酮酸联合缬沙坦治疗,对比两组患者临床疗效。结果观察组治疗总有效率为95.00%,明显高于对照组的77.50%,差异有统计学意义(P<0.05)。观察组FPG、BUN、Cr、24h尿蛋白量等指标明显优于对照组,差异有统计学意义(P<0.05)。复方α酮酸联合缬沙坦治疗早期DN,疗效安全,可改善各项实验室指标,控制肾脏损害进展,值得临床推广。
Objective To explore the influence of respiratory function training on pulmonary function of patients with pneumoconiosis.Methods One hundred patients with pneumoconiosis hospitalized in our department between June 2011 and September 2012 were chosen as the research subjects.According to the method of random digits table,they were equally and randomly divided into contrast group and observation group.Patients in both the two groups were given routine treatment and nursing and health education,while patients in the observation group adopted respiratory training with lung functional exerciser in addition.Then we observed the forced expiratory volume in one second(FEV_1),vital capacity,maximal voluntary ventilation,forced vital capacity,classification of conscious shortness of breath and shortness of breath as well as classification of activities of daily living in the patients before and after training in both the two groups.Results After 6 months,lung function index,classification of conscious shortness of breath and shortness of breath as well as classification of activities of daily living of patients in the observation group improved a lot,which was significantly better than that in the contrast group(P0.05).Compared with the contrast group,the FEV_1[(2.75±0.43) L],vital capacity[(3.29±0.45)L]of patients in the observation group were significantly higher(P0.05).Compared with the contrast group,classification of conscious shortness of breath and shortness of breath(2.10±0.67),classification of activities of daily living(2.19±0.66) were also significantly different(P0.05).Conclusion Respiratory function training with lung functional exerciser can improve lung function of patients with pneumoconiosis,alleviate the degree of dyspnea,and enhance the quality of life.
目的:探讨血管紧张素Ⅱ受体拮抗剂对糖尿病肾脏的保护作用。方法 STZ尾静脉注射建立大鼠糖尿病模型。用免疫组化方法检测大鼠肾脏巨噬细胞的表达。比较血管紧张素Ⅱ受体拮抗剂治疗组与非治疗组肾脏CD68+巨噬细胞的表达。结果糖尿病成模后,巨噬细胞在肾间质的表达明显增加。血管紧张素Ⅱ受体拮抗剂治疗组较非治疗组肾间质巨噬细胞的浸润减少加(P<0.01),伴随蛋白尿的减轻。结论血管紧张素Ⅱ受体拮抗剂可减轻糖尿病大鼠肾脏炎症浸润。
Objective To explore and analyze the value of fasting plasma glucose(FPG)and HbA1con the diagnosis of type 2diabetes mellitus.Methods 100patients with type 2diabetes and 100patients without type 2diabetes were included in the present study.Fasting blood sugar and HbA1cof patients were tested.The specificity and sensitive of fasting blood sugar and HbA1cwere counted.The accuracy of fasting blood sugar and HbA1con type 2diabetes mellitus were analyzed.Results The sensitive of FPG on type 2diabetes mellitus diagnose was 99%and the specificity was 93%. The sensitive of HbA1cdiagnose wss 95% and the specificity was 92%.The specificity and sensitive of fasting blood sugar and HbA1cwere no difference and they were similar to the diagnosis standard(P0.05).Conclusion The specificity and sensitive of HbA1cin clinical diagnosis of type 2diabetes and fasting blood sugar in the diagnosis of diabetes are significant difference.The result is agreeable to practical situation and has high diagnosis value.
Objective To explore the therapeutic effect of plasma exchange in the treatment of patients with medicamentosa-like dermatitis due to trichloroethylene (DMLT) accompanied with severe hepatitis. Methods Twenty-one patients were treated with plasma exchange combined with conventional therapy. Hepatic function markers, coagulation tests and changes of clinical symptoms were compared. Results The patients’ alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, tumor necrosis factor-a, prothrombin time, and albumin were 1176.2±243.50 U/L, 897.30±98.62 U/L, 327.50 ±137.70 mmol/L, 181.43±89.32 mmol/L, 38.63±8.42 pg/mL, and 20.32±5.06 g/L, respectively, before treatment, and were 384.61±78.60 U/L, 223.81±65.32 U/L, 132.45±69.57 mmol/L, 98.78±78.39 mmol/L, 9.84±2.69 pg/mL, and 32.78±4.59g/L (P 0.05), respectively, with the improvement of clinical symptoms after plasma exchange treatment. Activated partial thromboplastin time, thrombin time, and fibrinogen were 59.81±11.33 S, 26.7±10.42 S, and 1.47±0.86 g/L, respectively, before treatment, and were 55.47±24.36 S, 23.32±5.07 S, and 1.59±0.55 g/L, respectively, after plasma exchange treatment, but without statistical significances (P0.05). Twenty cases (95.2%) survived, and one patient died of pulmonary nocadia infection. Plasma exchange was totally performed 81 times in the 21 patients, with the occurrence of adverse reactions in 2 times. Conclusions Plasma exchange is safe and effective in the treatment of patients with DMLT.
目的 评价各种危险因素与缺血性肾病的关系,从而有效地预防及早期干预,减缓终末期肾病的发生.方法 选取收治的33例缺血性肾病患者,收集其生活习惯、既往史、家族史、临床资料、合并症.结果 缺血性肾病的发生和年龄、高血压、糖尿病、高血脂、动脉硬化、肥胖、吸烟等因素密切相关.结论 缺血性肾病的主要危险因素包括:慢性心功能不全、高血压、高血脂、糖尿病、肺部感染、抗凝治疗、肾动脉血管支架植入.有效地预防及早期干预高血压、糖尿病、高血脂等因素,纠正心功能不全及积极控制感染是降低缺血性肾病和减缓慢性肾衰竭发生的有效途径.
Objective To investigate whether high glucose up-regulate the expression of TLR2 on NRK-52E cells.Methods Rat renal proximal tubular epithelial cell line NRK-52E cells were cultured in DMEM supplemented with 10% FCS.Experiments were conducted in FBS-free medium containing various concentrations of glucose.Western Blot was used for measuring TLR2 protein.RT-PCR was used for measuring MCP-1mRNA expression.Results There was the expression of TLR2 in the renal tubular epithelial cell.The expression of TLR2 protein and MCP-1 mRNA significantly increased on NRK-52E cells under hyperglycemic conditions.Conclusion High glucose induced the expression of TLR2 and MCP-1 on NRK-52E cells,which induce the increase of chemotactic factor.
Objective To investigate whether the Toll-like receptor 4(TLR4)signaling is activated in diabetic nephropathy.And to investigate the relationship between TLR4 expression and renal macrophage infiltration. Methods Diabetes was induced by a single intravenous injection of streptozotocin.Immunohistochemical method was used for measuring macrophage infiltration and TLR4expression.Western Blot was used for measuring TLR4protein.RT-PCR was used for measuring TLR4mRNA expression. Results In diabetic rats,there was a significant up-regulation of TLR4protein and mRNA expression in the kidney.In the DM group,the expression of renal TLR4/β-actin in the 2nd,4th,and 8th weeks was higher than in the NC group;the expression of renal TLR4/GAPDH mRNA in the 2nd,4th,and 8th weeks was higher than in the NC group;and the renal macrophage infiltration in the kidney in the 4th and 8th weeks was more than in the NC group. Conclusion Enhanced renal expression of TLR4is associated with inflammatory infiltration in diabetic nephropathy.
Background/Aims: Inflammation is implicated in the pathogenesis of diabetic nephropathy (DN). This study examined the role of Toll-like receptor 2 (TLR2) in the progression of renal injury in a model of rat DN. Methods: DN was induced by intravenous injection of streptozotocin and rats were sacrificed at week 2, 4 and 8. Functional and pathologic markers, inflammatory infiltration, expression of TLR2, MCP-1, MyD88, HSP70, HMGB1 and activation of NF-ĸB were assessed. The effects of glucose on the expression of TLR2 by renal tubular epithelial cells were also examined in vitro. Results: The expression of TLR2 mRNA and protein level was significantly upregulated in the kidneys of diabetic rats (p < 0.01), which was associated with increased renal expression of MyD88 and MCP-1, activation of NF-ĸB and infiltration of macrophages. The expression of HSP70 and HMGB1, endogenous ligands of TLRs, was also significantly upregulated in the kidneys of diabetic rats. In human renal biopsy of DN, there was prominent expression of TLR2 in both the glomeruli and tubulointerstitium. In vitro study showed that high glucose induced the expression of TLR2 mRNA by NRK-52E cells (p < 0.01). Conclusions: Enhanced renal expression of TLR2 is associated with inflammatory infiltration in DN.