摘要:目的: 探讨激活转录因子(ATF1)在血管紧张素Ⅱ(AngⅡ)诱导血管平滑肌细胞(VSMCs)中NOX1基因表达增加的作用。 方法 :体外培养大鼠主动脉VSMCs,用荧光实时定量逆转录PCR(Realtime RTPCR)检测NOX1基因表达的量,Western Blot检测ATF1蛋白在AngⅡ的刺激是否引起NOX1基因的高表达并用RNA干扰(RNAi)技术转染VSMCs使ATF1基因沉默来观察NOX1的表达。 结果 :AngⅡ能够诱导 NOX1基因的表达增加以及增强ATF1的磷酸化及活性,ATF1基因沉默反过来可抑制AngⅡ诱导的NOX1基因表达的增加。 结论 :在大鼠的VSMCs中,ATF1是介导NOX1基因表达的一个必须的转录因子。Abstract: Objective: To detect the role of activating transcription factor (ATF1) involved in angiotensinⅡ(AngⅡ) stimulated NOX1 gene expression.Methods :Rat aortic vascellum smooth muscle cells(VSMCs) were cultured in vitro.Use Realtime RTPCR to measure the expression of NOX1 gene.Western Blot Analysis was carried out to test the activity of ATF1 protein. RNA interference was used and transfected into VSMCs to knockdown ATF1 gene expression, and then measured NOX1 gene expression.Results : AngⅡ stimulated NOX1 gene expression and phosphorylation of ATF1 Gene silencing of ATF1 attenuated the upregulation of NOX1 mRNA by AngⅡ. Conclusion :ATF1 is an essential transcription factor that mediates expression of NOX1 gene in VSMCs by AngⅡ.
摘要:目的: 探讨在血管紧张素Ⅱ(AngⅡ)诱导血管平滑肌细胞(VSMCs)NOX1基因表达增加中线粒体所起的作用。 方法 :体外培养大鼠主动脉VSMCs,用线粒体呼吸链的抑制剂阻断线粒体的作用,用荧光实时定量PCR检测NOX1基因表达的量。 结果 :AngⅡ能够诱导 NOX1基因的表达增加,线粒体呼吸链的抑制剂能够抑制上述这一作用。 结论 :在大鼠的VSMCs中,AngⅡ诱导NOX1的增加通过线粒体呼吸的作用。Abstract: Objective: To detect the role of mitochondria involved in Angiotensin Ⅱ(Ang Ⅱ) induced NOX1 gene expression. Methods :Rat aortic vascellum smooth muscle cells(VSMCs) were cultured in vitro,and were treated with or without some inhibitors of complexs in mitochondrial respiratory chain. Realtime RTPCR was used to calculate the expression of NOX1 mRNA. Results :AngⅡ stimulated NOX1 gene expression,while some inhibitors of complexs in mitochondrial respiratory chain attenuated this progress.〖WTHZ〗Conclusion : Mitochondrial respiratory chain mediates expression of NOX1 gene in VSMCs by AngⅡ.
Objective To investigate the role of angiotensin-II type 1 receptor ( AT1) antagonist in treatment of acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods Animal model of ALI/ARDS was induced by cecal ligation and perforation ( CLP) . ALI/ARDS animals received a separate intraperitoneal injection of several concentrations( 5, 10, 15, 20, 25 mg/kg) of AT1 inhibitor losartan after CLP, then the changes of lung injury and 7-day survival were measured. Results Oxygenation index and lung wet to dry weight ratio ( W/D) showed an improving trend when losartan was administered at doses of 5 to 15 mg/kg in ALI/ARDS rats, but aggravated above the dose of 15 mg/kg. Losartan ( 15 mg/kg) treatment significantly alleviated pulmonary edema after CLP operation, and decreased serumlevels of TNF-α, IL-6, andIL-1β [ TNF-α: ( 554. 1 ±62. 7 ) pg/mL vs. ( 759. 2 ±21. 5 ) pg/mL, P lt; 0. 01; IL-6: ( 1227. 3 ±130. 0) pg/mL vs. ( 2670. 4 ±174. 1) pg/mL, P lt; 0. 01; IL-1β: ( 444. 0 ±38. 6) pg/mL vs. ( 486. 6 ±61. 7)pg/mL, P lt; 0. 05] . 7-day survival rate also increased in losartan treatment group at a dose of 15 mg/kg( 6. 7% vs. 0 ) . Conclusions The AT1 inhibitor, losartan, can significantly prevent lung injury in ALI/ARDS after CLP, and improve the 7-day survival rate.
目的:探讨血管紧张素Ⅱ受体拮抗剂(ARB)对PAF患者P波离散度的影响。方法:观察48 例阵发性AF患者的最宽P 波和P 波离散度,并与ARB干预治疗3 个月后进行对比分析。结果:ARB治疗3个月后最宽P波、P 波离散度及P 波离散度≥40 ms的例数与治疗前比较差异有统计学意义 (Plt;0.05或lt;0.01)。结论:ARB能减轻PAF患者心房结构重构及电重构,减少AF的发生。
ObjectiveTo investigate the optimal administration combination of β-aminopropionitrile (BAPN) and Angiotensin Ⅱ (Ang-Ⅱ) in the establishment of SD rat aortic dissection (AD) model and the related complications. MethodsForty-two three-week-old male SD rats were randomly divided into 7 groups: a group A (0.25% BAPN), a group B (0.40% BAPN), a group C (0.80% BAPN), a group D [1 g/(kg·d) BAPN], a group E [1 g/(kg·d) BAPN+1 μg/(kg·min) saline], a group F [1 g/(kg·d) BAPN+1 μg/(kg·min) Ang-Ⅱ] and a group G (control group). There were 6 rats in each group. The intervention period was 4 weeks (groups E and F were 4 weeks+5 days). Rats were dissected immediately if they died during the experiment. After the intervention, the surviving rats were sacrificed by pentobarbital sodium, and the whole aorta was separated and retained. Hematoxylin-eosin staining was used to observe the changes of aorta from the pathological morphology. ResultsThere was no statistical difference in the survival rate among the groups after 4 weeks of BAPN intervention (P>0.05). After 5 days of mini-osmotic pumps implantation, the survival rate of rats was higher in the group E than that in the group F (P=0.008), and the incidence of AD in the group E was lower than that in the group F (P=0.001). BAPN could affect the food and water intake of rats. After BAPN intervention for 4 weeks, the body weight of rats in the group G was higher than those in the intervention groups (P<0.05). BAPN combined with Ang-Ⅱ could make the aortic intima thick, elastic fiber breakage, arrangement disorder, and inflammatory cell infiltration in rats, which conformed to the pathological and morphological changes of AD. BAPN could also affect mental state and gastrointestinal tract. ConclusionThe combination of BAPN [1 g/(kg·d)] and Ang-Ⅱ [1 μg/(kg·min)] can stably establish AD model in rats, which will provide a stable carrier for further study of the pathogenesis and therapeutic targets of AD. However, the complications in this process are an unstable factor. How to balance the influence of BAPN on other tissues and organs in the process of AD model establishment remains to be further studied.
Objective To systematically review the efficacy of total glycosides extracted from Rehmannia glutinosa Libosch leaf in the treatment of diabetic nephropathy. Methods Databases including PubMed, EMbase, MEDLINE, The Cochrane Library, Web of Science, CNKI, WanFang Data and VIP were electronically searched to collect randomized controlled trials of total glycosides from Rehmannia glutinosa Libosch for diabetic nephropathy from inception to May 30th, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. RevMan 5.4 software was then used to perform meta-analysis. Results A total of 7 RCTs involving 504 patients were included. The results of meta-analysis showed that there were no significant differences in creatinine levels (MD=−1.71, 95%CI −3.97 to 0.56, P=0.14) and urea (MD=−0.18, 95%CI −0.44 to 0.08, P=0.19) between the two groups. In terms of regulating proteinuria, the urinary albumin excretion rate (MD=−39.41, 95%CI −48.46 to −30.36, P<0.000 01), urinary microalbumin (MD＝−9.94, 95%CI −12.16 to −7.73, P<0.000 01), and 24-hour urinary protein (MD=−0.67, 95%CI −0.85 to −0.49, P<0.000 01) were all lower in the treatment group compared with control group. However, there were no differences between groups in terms of blood glucose metabolism as indicated by changes in levels of the long-term blood glucose metabolism indicator (HbA1c: MD=−0.16, 95%CI −0.67 to 0.35, P=0.53). Only one study suggested that short-term blood glucose metabolism indicators, fasting blood glucose and postprandial blood glucose levels were not different between groups. In terms of blood lipid metabolism, only one study suggested glycoside treatment produced lower serum levels of cholesterol and triglycerides compared with control group. Conclusions Current evidence suggests that adjunctive therapy with total Rehmannia glutinosa Libosch glycosides can benefit diabetic nephropathy patients more than angiotensin II receptor inhibitor or pancreatic kininogen by alleviating proteinuria and likely improving lipid metabolism. However, no benefit is observed in terms of renal function improvement or blood glucose metabolism. Due to limited quality and quantity of included studies, more high-quality studies are required to verify the above conclusions.
Objective To explore the role of renin-angiotensin system( RAS) in acute lung injury( ALI) /acute respiratory dysfunction syndrome( ARDS) by using amouse cecal ligation and puncture ( CLP)model.Methods The ALI/ARDS animal models were assessed bymeasuring blood gas, wet/dry lung weight ratio( W/D) , and lung tissue histology 18 hours after CLP operation. After the ALI/ARDS models was successfully established, immunohistochemistry, western blotting and radioimmunity were used to investigate the changes of several key enzymes of RAS, such as ACE, ACE2 and Ang Ⅱ. In addition, two groups of animals received a separate intraperitoneal injection of angiotensin-converting enzyme ( ACE) inhibitor captopril or recombinant mouse ACE2 ( rmACE2) after CLP, then the changes of RAS in ALI/ARDS modelswere observed. Results The extensive lung injuries can be observed in the lung tissues from CLP-treated animals 18 hours after operation. The CLP-induced ALI/ARDS led to an increase in the wet/dry weight ratio of the lung tissues, and a decrease in the PaO2 /FiO2 [ ( 194. 3 ±23. 9) mm Hg vs ( 346. 7 ±20. 5) mm Hg,P lt;0. 01] . Immunohistochemistry and western blotting tests of the lung tissues from CLP-treated animals showed a decrease in the ACE2 protein level. However, in both the CLP and sham mice there were no significant differences between the two groups. CLP markedly increased Ang Ⅱ level in lungs and plasma of mice, and RAS drugs significantly impacted the Ang Ⅱ levels of mice. Compared with the CLP group,captopril or rmACE2 led to a decrease of the Ang Ⅱ level in mice [ Lung: ( 1. 58 ±0. 16) fmol /mg,( 1. 65 ±0. 21) fmol /mg vs ( 2. 38 ±0. 41) fmol /mg; Plasma: ( 178. 04 ±17. 87) fmol /mL, ( 153. 74 ±10. 24) fmol /mL vs ( 213. 38 ± 25. 44) fmol /mL] . Conclusions RAS activation is one of the characteristics of CLP-induced ALI/ARDS in mice models. ACE and ACE2 in RAS have a different role in the regulation of AngⅡ synthesis, while ACE has a positive effect in generating AngⅡ, and ACE2 shows a negative effect.