肾素-血管紧张素系统与糖尿病的研究进展

<正>经典的肾素-血管紧张素系统(RAS)由肝脏合成的血管紧张素原(AGT)、肾脏近球细胞合成的肾素、肺血管床内皮细胞表面的血管紧张素转换酶(ACE)、血管紧张素Ⅱ(AngⅡ)及其受体组成。在众多的血管紧张素家族成员中,AngⅡ的作用最为重要。在循环系统中,AngⅡ可与血管紧张素1型受体(AT1R)及血管紧张素2型受体(AT2R)结合发挥作用,其中AT1R的作用更为广泛和重要。过去认为,RAS为人体内重     

PI3K/AKT通路与TRPC6通道在Ang Ⅱ诱导足细胞损伤中的相互作用

目的 探讨磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)通路与瞬时受体电位阳离子通道蛋白6(TRPC6)在血管紧张素Ⅱ(Ang Ⅱ)诱导的肾小球足细胞损伤过程中的作用及其可能机制.方法 体外培养小鼠肾小球足细胞,分别利用Ang Ⅱ、氯沙坦、PI3K/AKT通路抑制剂(LY294002)、TRPC6通道阻滞剂(SKF96365)进行处理,将细胞分为空白对照组、Ang Ⅱ组、Ang Ⅱ+氯沙坦组、氯沙坦组、Ang Ⅱ+LY294002组、LY294002组、Ang Ⅱ+SKF96365组、SKF96365组,采用qRT-PCR检测各分组细胞TRPC6 mRNA的变化.采用Western blot检测各分组细胞AKT、磷酸化蛋白激酶B(p-AKT)、TRPC6蛋白质表达的变化.采用Hoechst 33258染色法检测各组足细胞凋亡情况.结果 与空白对照组相比,Ang Ⅱ组AKT磷酸化水平降低,TRPC6的表达升高,足细胞凋亡增加(P＜0.05).与Ang Ⅱ组相比:Ang Ⅱ+SKF96365组AKT磷酸化水平升高,TRPC6的表达下降,足细胞凋亡减少(P＜0.05);Ang Ⅱ+LY294002组AKT磷酸化水平减少,足细胞凋亡增加(P＜0.05);Ang Ⅱ+氯沙坦组AKT磷酸化水平升高,TRPC6的表达下降,足细胞凋亡减少(P＜0.05).结论 Ang Ⅱ可能通过激活TRPC6通道进而抑制PI3K/AKT通路的激活而导致足细胞损伤.     

血管紧张素Ⅱ及其受体在疼痛中的研究进展

血管紧张素Ⅱ(AngiotensinⅡ,AngⅡ)是肾素-血管紧张素系统(the renin-angiotensin system,RAS)的主要活性肽,主要作用于AT1R(angiotensin Ⅱ receptor)和AT2R(angiotensin Ⅱ type 2 receptor)两种受体,在人类及大鼠组织中广泛表达。近年来发现AngⅡ及其受体还参与疼痛的调节,其受体拮抗剂可应用与临床疼痛的治疗。本文就血管紧张素Ⅱ及其受体在疼痛中的研究进展进行综述。     

血管紧张素-(1-7)研究进展

肾素-血管紧张素系统(renin-angiotensin system，RAS)是机体活动调节的重要组成部分，在机体局部和全身的激活可引起多种生理病理变化，该系统包括肾素、血管紧张素原(angiotensinogen，AGT)、血管紧张素-Ⅰ(Ang-Ⅰ)、血管紧张素-Ⅱ(Ang-Ⅱ)和RAS系统的各种旁路代谢产物，如血管紧张素-(1-7)[angiotensin-(1-7)，Ang-(1-7)]、Ang-(3-8)、Ang-(2-8)、Ang-(1-6)等，以及血管紧张素受体，血管紧张素转换酶(ACE)。以     

血管紧张素Ⅱ及其受体拮抗剂对肝星状细胞Ⅲ型胶原合成的影响

目的 观察血管紧张素Ⅱ及其受体拮抗剂对体外培养的肝星状细胞Ⅲ型胶原蛋白合成及其mRNA表达的影响.方法 采用HSC-T6肝星状细胞系作为活化的肝星状细胞的研究模型.将培养的肝星状细胞随机分为对照组、血管紧张素Ⅱ(AngⅡ)组、受体拮抗剂(AT1RA)组和血管紧张素Ⅱ 受体拮抗剂(AngⅡ AT1RA)组.采用ELISA法检测细胞培养上清液中Ⅲ型胶原蛋白的含量;RT-PCR法检测肝星状细胞中Ⅲ型胶原mRNA的表达.结果 细胞培养上清液中Ⅲ型胶原蛋白的含量对照组、AngⅡ组和AngⅡ AT1RA组分别为(6.301±0.432)ng/ml、(7.356±0.237)ng/ml和(6.263±0.236)ng/ml,AngⅡ组高于对照组(P＜0.05),AngⅡ AT1RA组显著低于AngⅡ组(P＜0.05).肝星状细胞Ⅲ型胶原mRNA的表达水平对照组、AngⅡ组和AngⅡ AT1RA组分别为2.317±0.015、2.643±0.057和2.330±0.036,AngⅡ组高于对照组(P＜0.05),AngⅡ AT1RA组显著低于AngⅡ组(P＜0.05).结论 血管紧张素Ⅱ能够促进肝星状细胞Ⅲ型胶原蛋白的合成及其mRNA的表达,而血管紧张素Ⅱ1型受体拮抗剂能够明显抑制这一作用.     

中枢血管紧张素转化酶2-血管紧张素1-7-Mas轴对心血管活动的调节

肾素-血管紧张素系统(renin-angiotensin system,RAS)对于血压的调节、电解质和体液平衡的维持均有重要作用.血管紧张素转化酶(angiotensin converting enzyme,ACE)、血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)及其受体AT1R组成了经典的ACE-AngⅡ-AT1R轴.而近年来发现的存在于该系统的许多新成分,特别是Mas受体和血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2),它们与Ang 1-7共同构成ACE2-Ang 1-7-Mas轴,拮抗经典的ACE-AngⅡ-AT1R轴,成为RAS的新分支.     

肝癌干细胞样细胞的分离及其耐药性受PI3K/Akt通路调节

目的 分离肝癌干细胞样细胞,初步探讨PI3 K/Akt通路调节其对化疗药物阿霉素的敏感性.方法 将人肝癌细胞株PLC、HepG2、Hep3B置于无血清条件培养基中培养,形成细胞球,选用PLC细胞株进行后续实验.采用流式细胞仪、克隆形成实验、SCID小鼠体内成瘤实验鉴定PLC细胞球(肝癌干细胞样细胞)的肿瘤干细胞特性.MTT法、流式细胞仪测定PLC细胞球对化疗药物阿霉素的敏感性.流式细胞仪分析加入PI3 K/Akt通路特异性抑制剂LY294002、阿霉素共同孵育细胞球后,其凋亡率的变化.Western blot法比较PLC细胞球、PLC贴壁细胞中p-Akt1(Ser473)蛋白分子表达量及加入抑制剂LY294002作用于细胞球后,p-Akt1(Ser473)、Akt1蛋白分子表达量的变化.结果 肝癌干细胞标志物CD90在细胞球中的表达较贴壁细胞显著升高(P＜0.01).细胞球的克隆形成数目(123.00±28.48)为贴壁细胞(56.33±7.37)的2.18倍(P＜0.05).同样细胞数接种于SCID小鼠皮下7周后,细胞球的致瘤率明显大于贴壁细胞.以5μg/mL的阿霉素分别处理细胞球和贴壁细胞48 h后,细胞球的增殖率明显高于贴壁细胞[(71.83±12.30)％ vs (45.68±5.95)％,P ＜0.05],凋亡率显著低于贴壁细胞[(11.73 ±3.77)％ vs (41.22±6.73)％,P＜0.01],而以阿霉素5μg/mL和LY294002共同孵育细胞球后,其凋亡率[(35.44±6.65)％]显著增加(P＜0.01).Western blot检测到细胞球的p-Akt1(Ser473)蛋白分子表达量显著高于贴壁细胞(P＜0.01),加入抑制剂LY294002处理细胞球后,p-Akt1(Ser473)蛋白表达量明显降低(P＜0.05),Akt1的表达量无明显变化(P＞0.05).结论 肝癌干细胞样细胞对化疗药物阿霉素具有耐药性,其耐药机制与Akt信号通路第473位点磷酸化Akt1分子有关.     

核转录因子YY1对缺血缺氧诱导的心肌细胞凋亡的影响及其机制

目的 探讨核转录因子阴阳1 (yin yang 1,YY1)对体外缺血缺氧诱导的心肌细胞凋亡的抑制作用及其机制.方法 体外分离培养新生大鼠心肌细胞,利用无糖培养基及含95％ N2+5％ CO2混合气体的缺氧装置(Billups-rothenberg)诱导建立缺血缺氧心肌细胞凋亡模型,通过建立过表达YY1重组质粒并将其转染入心肌细胞内,观察YY1对缺血缺氧诱导的心肌细胞凋亡的影响.实验分为对照组、YY1组、缺血缺氧组、缺血缺氧+YY1组、缺血缺氧+LY294002组、缺血缺氧+YY1+LY294002等6组(n=4).CCK-8法检测各组心肌细胞活力,TUNEL法检测各组心肌细胞凋亡情况,fQT-PCR检测YY1 mRNA表达水平,Westem blot法检测YY1、磷酸化丝氨酸苏氨酸激酶(p-Aktser473)及生存素(Survivin)蛋白表达水平.结果 与对照组相比,缺血缺氧组在缺血缺氧刺激6h后心肌细胞活力下降、凋亡率明显增高[(0.55 ±0.02) vs (1.14±0.02)、(38.25 ±1.65)％ vs (1.38±0.15)％,P＜0.01].缺血缺氧前预转染YY1重组质粒后,与缺血缺氧组相比,缺血缺氧+YY1组心肌细胞活力上升、凋亡率降低、p-Aktser473和Survivin蛋白表达增加[(0.78 ±0.03) vs (0.55 ±0.02)、(14.50±1.56)％ vs (38.25±1.65)％、p-Aktser473相对灰度值:(0.82±0.03) vs (0.28 ±0.03)、Survivin相对灰度值:(0.93 ±0.02) vs (0.36±0.02),P＜0.01].经PI3K/Akt信号通路特异性抑制剂LY294002干预后,缺血缺氧+ YY1+LY294002组与缺血缺氧+YY1组相比,心肌细胞活力下降、凋亡率增加、p-Aktser473和Survivin蛋白表达显著降低[(0.62 ±0.02) vs (0.78 ±0.03)、(27.75±1.12)％vs (14.50±1.56)％,p-Aktser473相对灰度值:(0.43 ±0.02)vs(0.82±0.03),Survivin相对灰度值:(0.27 ±0.02) vs (0.93 ±0.02),P＜0.01].结论 核转录因子YY1可抑制缺血缺氧诱导的心肌细胞凋亡,且该作用与PI3K/Akt信号通路的激活相关.     

罗格列酮对心肌梗死大鼠血流动力学及肾素-血管紧张素系统的影响

[目的]探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动药罗格列酮对心肌梗死大鼠血流动力学及肾素-血管紧张素系统的影响.[方法]45只SD大鼠随机分为假手术组(9只)和心肌梗死组(36只),将制作心肌梗死模型后24 h仍存活的21只SD大鼠随机分为心肌梗死对照组(10只)和罗格列酮组(11只).罗格列酮组术后24 h开始给予罗格列酮3 mg/(kg·d)共8周.8周后测定血流动力学,称量心脏、左室、右室、肺和肝质量,用放射免疫法测定血浆及心肌血管紧张素Ⅱ、醛固酮以及血浆肾素活性.[结果]与心肌梗死对照组相比,罗格列酮组明显改善左室±dp/dtmax[(-1 898±383)mmHg/s vs(-2 981±258)mmHg/s,P＜0.05,(2 110±461)mmHg/s vs(3 625±221)mmHg/s,P＜0.05)];显著降低肺体比和肝体比(P＜0.05);明显抑制心肌局部血管紧张素Ⅱ[(0.23±0.02)ng/mg pro vs(0.14±0.01)ng/mg pro,P＜0.05]及醛固酮水平[(0.31±0.05)ng/mg pro vs(0.19±0.04)ng/mg pro,P＜0.05)],而对血浆肾素活性、血管紧张素Ⅱ及醛固酮无明显影响(P＞0.05).[结论]PPARγ激动药罗格列酮改善心肌梗死大鼠血流动力学,抑制心肌局部肾素-血管紧张素系统.     

重症中暑对大鼠心肌肾素-血管紧张素系统的影响

目的：探讨重症中暑对大鼠心肌肾素-血管紧张素系统的影响。方法选用雄性Wistar大鼠24只,应用随机数表法将大鼠分为正常对照组、热打击后2 h组、热打击后24 h组,每组8只。采用放射免疫法测定大鼠血浆和心肌肾素及血管紧张素Ⅱ活性,采用免疫组化法测定心肌血管紧张素Ⅱ-1、2型受体(AT1R、AT2R)蛋白表达水平。结果大鼠热打击后60 min左右肛温达到42℃,77 min左右平均动脉压下降25 mmHg,此时即重症中暑造模成功。热打击后2 h及24 h组大鼠血浆和心肌肾素-血管紧张素系统显著激活[血浆RA：(2237.0±173.2)、(1498.0±172.3) vs (785.4±43.2),P<0.05;血浆AngⅡ：(143.4±19.8)、(76.8±21.6) vs (42.8±8.6),P<0.05;心肌RA：(10.63±0.59)、(8.49±0.92) vs (1.66±0.38) P<0.05;心肌AngⅡ：(279.9±11.3)、（212.5±10.1) vs (39.6±6.3) P<0.05];热打击后24 h组大鼠血浆和心肌肾素-血管紧张素系统仍处于激活水平,但较热打击后2 h组明显下降[血浆RA：(2237.0±173.2) vs (1498.0±172.3),P<0.05;血浆AngⅡ：(143.4±19.8) vs (76.8±21.6),P<0.05;心肌RA：(10.63±0.59) vs (8.49±0.92),P<0.05;心肌AngⅡ：(79.9±11.3) vs (212.5±10.1),P<0.05]。热打击后2 h及24 h组心肌AT1R蛋白表达明显上调[(49.8±14.1)、(52.6±15.8) vs (13.0±5.0),P<0.05];热打击对AT2R蛋白表达无影响[(14.1±6.2)、(16.8±7.3) vs (9.8±4.5),P>0.05]。结论重症中暑早期能够导致大鼠心肌肾素-血管紧张素系统显著激活。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Acupuncture Treatment of Vomiting

CASE HISTORY A female patient, 46 years old, head of the foreign affairs department of a certain university in Beijing, paid her first visit on October 9, 2006, with the chief complaint of vomiting for one month. She got vomiting after meals in early September. Before that, she had discomfortable sensation in the stomach due to angry with others, but she didn't pay much attention. Later, it developed into vomiting after eating. After the vomiting, the discomfort would be relieved, but with slight hypodynamia. She was once diagnosed as having 'neurogenic vomiting'. Having taken some western and Chinese drugs, the above symptoms were a little bit improved, but she would have nausea upon eating and with regurgitation. Because of the fear for vomiting, she did not dare to have food intake, with body weight reduction of 6 kilos in one month.     

Qiu Baoguo''''s Experience in Treating Consumptive Syndromes after Radio-Chemotherapies

Radiotherapy and chemotherapy are the important modern medical therapies for malignant tumors,yet they can also bring about serious local and systemic toxic side reactions so to decrease the patient;'s life quality,manifested by a series of consumptive symptoms.Having engaged in the combined work of Chinese and western medicine for nearly 50 years,the research fellow Qiu Baoguo in Henan Provincial Academy of TCM has developed his unique views on the TCM study of consumptive syndromes.The author of this essay had once the fortune tO follow Dr.Qiu in clinic,and specially would like to introduce in the following Dr.Qiu's experience in treating consumptive syndromes after radio-chemotherapies for patients with malignant tumor.     

Insomnia Due to Deficiency of Both the Heart and Spleen Treated by Acupuncture-Moxibustion and Chinese Tuina

OBJECTIVE: To observe therapeutic effects of the comprehensive therapy of acupuncture-moxibustion and Chinese Tuina for treatment of insomnia due to deficiency of both the heart and spleen. METHODS: 92 cases were divided randomly into the treatment group (treated by acupuncture-moxibustion and Chinese Tuina) and the control group (treated by acupuncture-moxibustion). RESULTS: The therapeutic effect of the treatment group was obviously superior to that of the control group (the CHI2 test showed P < 0.01). CONCLUSIONS: The comprehensive therapy of acupuncture-moxibustion and Chinese Tuina can give marked therapeutic effects for treatment of insomnia due to deficiency of both the heart and spleen.     

Analysis of CK-19,PDX-1,Nestin,Ngn3 in different donor islet purity in rats

Objective: To investigate if there are the CK-19, PDX-1, Nestin, Ngn3 positive cells in the donor islets of different purity in rats. Methods: Thirty male adult SD rats were randomly divided into 3 groups. Islets were isolated using digestion by ductal injection of collagenase. Group Ⅰ (n=10): Separating cell preparations were not purified, Group Ⅱ(n=10): Islet sediment was purified with 25% Ficoll400 ,Group Ⅲ (n=10): Islet sediment was purified with 25% and 11% Ficoll-400. The levels of protein of CK-19, PDX-1, Nestin and Ngn3 were detected by immunohistochemistry and the mRNA of CK-19, PDX-1, Nestin, Ngn3 was amplified by RT-PCR. Results: After two different purification methods applied, three islet preparations of different purities were obtained. The difference of islet purity was significant among various groups (P＜0.05). Compared with group Ⅱ and group Ⅲ,the protein and mRNA of CK-19, PDX-1, Nestin,Ngn3 were both higher in group Ⅰ; group Ⅲ was poorly expressed. Conclusions: The three different islet purity donor islet have different CK-19, PDX-1, Nestin, Ngn3 positive cells within them, indicating that there are some islet stem cells in the purified donor islet.     

Dr.Zhang Ren''''s Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

Luo Lingjie''''s Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.