目的:观察抗纤灵对慢性肾功能衰竭(chronic renal failure,CRF)模型Smad2-KO小鼠心脏I型胶原(collagenⅠ,CoⅠ)、Ⅲ型胶原(collagenⅢ,CoⅢ)、血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(Interleukin-6,IL-6)水平的影响,探讨抗纤灵治疗CRF的作用机制.方法:将18只假手术Smad2-KO小鼠随机分为假手术组(蒸馏水0.5 mL,灌胃)、抗纤灵假手术组(抗纤灵复方20 g/kg,0.5 mL灌胃)、缬沙坦假手术组(缬沙坦20 mg/kg,0.5 mL灌胃),每组6只.将24只CRF模型Smad2-KO小鼠随机分为模型组(蒸馏水0.5 mL,灌胃)、抗纤灵模型组(抗纤灵复方20 g/kg,0.5 mL灌胃)、缬沙坦模型组(缬沙坦20 mg/kg,0.5 mL灌胃),每组8只.灌胃8周后取材,Elisa法检测心脏AngⅡ的水平,Western blot法测心脏CoⅠ、CoⅢ、TNF-α、IL-6的相对表达.结果:与假手术组比较,模型组的AngⅡ、CoⅠ、CoⅢ、TNF-α、IL-6均显著增高(P<0.01),缬沙坦假手术组的AngⅡ下降(P<0.05).与模型组比较,抗纤灵模型组的AngⅡ有改善(P<0.05),CoⅠ、CoⅢ、TNF-α、IL-6有显著改善(P<0.01).缬沙坦模型组的CoⅠ、CoⅢ、AngⅡ、TNF-α、IL-6均明显改善(P<0.01).抗纤灵模型组与缬沙坦模型组组间比较,缬沙坦在改善AngⅡ方面优于抗纤灵组(P<0.05),其余指标两组间比较差异无统计学意义(P>0.05).结论:抗纤灵可改善CRF模型Smad2-KO小鼠心脏病变的作用机制可能与降低炎症因子的表达、调节RAS和减少心脏胶原的过度沉积有关.
目的 观察超声引导联合介入技术在血液透析患者动静脉内瘘狭窄中的临床应用效果.方法 60例血液透析患者作为研究对象,随机分成对照组与观察组,各30例.对照组应用介入技术(经皮腔内血管成形术)治疗,观察组应用超声引导联合介入技术治疗,对比两组穿刺时间、手术时间、穿刺并发症发生率、术后瘘口血流量等指标.结果 观察组穿刺时间、手术时间分别为(5.19±1.93)、(61.05±13.56)min,均短于对照组的(8.41±5.65)、(71.62±17.83)min,差异具有统计学意义(P<0.05).观察组穿刺并发症发生率为3.33%,低于对照组的20.00%,差异具有统计学意义(P<0.05).观察组内瘘口血流量为(538.02±32.98)ml/min,高于对照组的(518.36±36.01)ml/min,差异具有统计学意义(t=2.2052,P<0.05).结论 超声引导联合介入技术在血液透析患者动静脉内瘘狭窄中的临床应用效果较好,可以缩短穿刺和手术时间,减少并发症的发生,值得临床推广应用.
慢性肾脏病(CKD)目前已成为全球威胁人类健康的公共卫生问题,我国成年人群中CKD的患病率为10.8%,CKD的知晓率仅为12.5%.而CKD进行性发展最终会进入终末期肾病.因此,加强对CKD的防治,已成为不可忽视的公共卫生问题之一.故早期发现、早期诊断、早期治疗、早期人为干预,延缓CKD进程就显得尤其重要.导师经过临床观察发现焦虑状态与CKD进展有关联性,有研究指出,CKD患者较正常人群更易发生焦虑;因此,对情绪因素的治疗应该成为CKD治疗的一个重要的组成部分.笔者通过探索性临床研究,初步观察精神、情绪因素(焦虑状态)在CKD慢性进程中的作用及其与CKD患者病情进展的相关性.为后续大规模的临床验证研究奠定基础,为临床制定针对CKD患者的心理健康管理策略提供依据.并以此课题引起医务工作人员对CKD患者心理健康方面的重视,对患者进行早期心理干预,以达到延缓CKD进展,改善CKD患者的生活质量的目的.
目的:采用单侧输尿管结扎(UUO)方法建立肾间质纤维化模型大鼠,观察刺梨黄酮对UUO模型大鼠肾组织中氧化应激指标及TGF-β1、TGF-βR Ⅰ的影响.方法:将60只SD雄性大鼠适应性喂养1周后,随机分为假手术组(生理盐水)、模型组(生理盐水)、刺梨大剂量组(刺梨冻干粉)、刺梨中剂量组(刺梨冻干粉)、氯沙坦钾组(氯沙坦钾)各12只;除假手术组外,各组均行单侧输尿管结扎术(UUo),假手术组只行输尿管分离,但不结扎.各组于分组当天,均以相对应的药物灌胃,疗程14 d.应用比色法、免疫组织化法,Western blotting等检测技术,观察大鼠肾组织丙二醛(MDA)和超氧化物歧化酶(SOD)含量以及肾组织TGF-β1、TGF-βR Ⅰ的表达.结果:与假手术组比较,模型组病理损伤程度显著增加,MDA含量增加、SOD含量降低(P<0.01),TGF-β1、TGF-βR Ⅰ的表达水平明显增加(P<0.05).与模型组比较各治疗组病理损伤减轻,MDA含量降低、SOD含量升高,TGF-β1、TGF-βR Ⅰ表达减少(P<0.05),跟剂量无关,中剂量组治疗疗效优于大剂量组(P<0.05).中剂量组与氯沙坦钾组比较差异无显著性(P>0.05).结论:刺梨黄酮与氯沙坦均能抑制单侧输尿管结扎肾间质纤维化大鼠的肾组织脂质过氧化物的产生,同时能增加抗氧化酶的含量,保护受损肾小管上皮细胞,有效改善肾脏纤维化病变,其机理可能与抗氧化应激、下调TGF-β1、TGF-βR Ⅰ的表达有关.
Objective To observe the effects of Cili freeze-dried powder on renal fibrosis and inflammatory factors in unilateral ureteral obstruction( UUO) model rats,and explore the intervention mechanism of Cili freeze-dried powder delaying the process of renal fibrosis. Methods The SD male rats were divided into four groups: sham operated group,model group,losartan potassium group,Cili freeze-dried powder group. The former two groups were given normal distilled water,and losartan potassium group and Cili freeze-dried powder group were treated with losartan potassium( 1 mg/100 g) and Cili freeze-dried powder( 300 mg/100 g) respectively. Model rats were sacrificed at 14 th day after first administration. The specimens were collected,and the pathological changes of renal tissue were observed. Immunohistochemical method was used to detect alpha-smooth muscle actin( α-SMA),collagen type Ⅲ( Col-Ⅲ),and Western blot was used to detect protein expression level of TGF-β1,NF-κB p65 and TLR2. Results Under light microscope,the renal tissue structure in the sham operated group was basically normal and there was no infiltration of inflammatory cells in the stroma,without Collagennous fiber or a little Collagennous fiber changes. The renal tissue structure in the model group was disor-dered,and a large number of inflammatory cell infiltration and obvious interstitial collagen deposits were seen in the interstitium of the kidney. As compared with model group,pathological changes were significantly alleviated in losartan potassium group and Cili freeze-dried powder group,and only a small amount of expression of α-SMA,Col-Ⅲ,TGF-β1,NF-κB p65 and TLR2 was detected in renal tissue in sham operated group. In the model group,the expression of these proteins increased significantly. As compared with the model group,α-SMA,Col-Ⅲ,TGF-β1,NF-κB p65 and TLR2 proteins were significantly down-regulated in the losartan potassium group and the Cili freeze-dried powder group( P <0. 01). As compared with the Losartan potassium group,the expression of TLR2 and NF-κB p65 proteins was significantly reduced in the Cili freeze-dried powder group( P < 0. 05),and there was no statistically significant difference in the expression of α-SMA,Col-Ⅲ and TGF-β1( P > 0. 05). Conclusions The Cili freeze-dried powder on immune renal tissue in the rat UUO model can modulate the local microenvironment,and can improve the renal fibrosis.
目的:探讨观察刺梨黄酮对UUO模型大鼠肾纤维化TGF-β1/Smads信号转导干预作用,并分析其机制.方法:将75只造模成功的肾纤维化大鼠随机分为5组,即假手术组、模型对照组、氯沙坦钾组、刺梨黄酮中剂量及大剂量组,每组各15只.氯沙坦钾组给予氯沙坦钾灌胃;刺梨黄酮中剂量及大剂量组分别给予刺梨黄酮灌胃.模型组和假手术组均同时给予同等容积的生理盐水.干预14 d后,观察24 hUpro、Scr、BUN,对比各组大鼠肾脏组织TGF-β1、Smad2/3、Smad7蛋白表达水平,分析刺梨黄酮对肾纤维化大鼠作用机制.结果:干预过程中,模型组和氯沙坦钾组各有1只大鼠死亡.模型组、氯沙坦钾组、刺梨黄酮中剂量和大剂量组24 hUpro、Scr和BUN水平较假手术组显著升高(P<0.01);治疗后氯沙坦钾组、刺梨黄酮中剂量和大剂量组较模型组显著降低;与氯沙坦钾组相比,刺梨黄酮中剂量组24 hUpro、Scr和BUN表达水平无明显差异(P>0.05).免疫组化显示模型组、氯沙坦钾组和刺梨黄酮不同剂量组中,各组TGF-β1、Smad2/3表达均明显高于假手术组(P<0.01),各治疗组的表达水平明显低于模型组(P<0.05).各组Smad7的表达均明显低于假手术组(P<0.01),各治疗组的表达水平明显高于模型组(P<0.05).与氯沙坦钾组比较,刺梨黄酮中剂量组TGF-β1、Smad2/3、Smad7表达水平无明显差异.结论:刺梨黄酮中剂量组可显著改善肾纤维化大鼠肾功能指标,推测和抑制TGF-β1、Smad2/3蛋白表达、激活Smad7蛋白表达有关.