脂肪间充质干细胞在心肌梗死治疗的研究进展

脂肪间充质干细胞（ adipose-derived mesenchymal stem cells ,ADSCS）是成体间充质干细胞的一种,来源丰富,全身各组织器官均可,取材方便,对人体创伤小,并且具有同其他干细胞（如骨髓间充质干细胞、脐血干细胞等）类似的多向分化潜能。心肌梗死是目前人类疾病中发病率及病死率高的病种,细胞治疗在这一领域中有很高价值,脂肪间充质干细胞因取材方便及多向分化潜能具有很大的应用前景,脂肪间充质干细胞在心肌梗死治疗中的对心肌保护机制成为一个研究热点。     

老龄兔骨髓间充质干细胞移植治疗心肌梗死最佳剂量的研究

目的 探讨老龄兔骨髓间充质干细胞移植治疗心肌梗死的最佳剂量,为细胞移植治疗心肌细胞坏死性相关疾病提供前期的实验依据.方法 选择≥36个月龄的新西兰大耳白兔30只,建立心肌梗死模型,将造模成功兔随机分为4组(空白对照组、4×104低剂量组、4×105中剂量组、4×106高剂量组),每组5只;在心肌梗死1天后,用微量注射器抽取200 μl密度为2×105/ml、2×106/ml、2×107/ml标记后的细胞悬液(剂量分别为4×104、4×105、4×106个),分别多点注射在心肌梗死区,空白对照组注射等量生理盐水,8 w后进行心功能参数、心脏房室瓣血流率及血液动力学指标检测.观察心肌梗死后相同时间,不同细胞剂量的移植对心功能的影响.结果 与对照组比较,4×104低剂量组细胞移植治疗后心功能虽有提高,但差异无显著性(P＞0.05);4×105中剂量组心功能参数、心脏房室瓣血流率及血液动力学指标高于对照组(P＜0.05);4×106高剂量组心功能参数、心脏房室瓣血流率及血液动力学指标明显高于对照组(P＜0.01);4×106高剂量组心功能参数、心脏房室瓣血流率及血液动力学指标高于4×105中剂量组(P＜0.05).结论 相同心肌梗死时间、不同移植细胞剂量时,以移植4×106个高剂量组心功能改善更明显.     

脂肪间充质干细胞移植对兔心梗后近期心功能的影响

目的: 观察脂肪间充质干细胞(ADMSCs)心肌内移植对兔心肌梗死(MI)后心力衰竭近期心功能的影响,并初步探讨其机制。方法: 将30只兔随机分为假手术组（只穿线不接扎）、对照组（心肌内注射IMDM培养基）及干细胞移植组（心肌内注射ADMSCs）,每组10只(n=10);结扎兔冠状动脉左前降支（LAD）制作急性MI模型,同时将6-二氨基-乙-苯茚二酮(DAPI)标记的ADMSCs注射到梗死区数个不同部位。造模前及移植后4周、8周,用超声心动图检测心功能,术后8周处死动物测量左室体质量指数及组织学观察,采用免疫荧光方法鉴定移植的细胞。结果: 移植后4周起,心功能指标明显改善(P<0.05),术后第8 周心功能指标改善更明显(P<0.01),左室重构程度也得到明显改善(P<0.01)。结论: 移植的ADMSCs可在宿主体内成活,并显著改善兔MI后的心功能。     

骨髓间充质干细胞移植治疗心肌梗死的新技术

骨髓间充质干细胞移植是治疗心肌梗死的新途径之一,其技术和方法不断发展。诸如建立更好的大型活体实验动物模型；改进对植入细胞的标记追踪技术；进一步研究细胞植入的适宜方式和时间等。骨髓间充质干细胞移植和基因疗法相结合可能得到叠加的治疗效果。     

自体骨髓间充质干细胞移植治疗心肌梗死的进展

心肌梗死可引起心肌细胞的丢失,进而引起心脏功能的下降,是心力衰竭最主要的病因。骨髓间充质干细胞（BM—MSCs）是一类具有横向分化为各系统器官和组织能力的干细胞,能补充丢失的心肌细胞并通过旁分泌等机制增强心功能,为心肌梗死提供一种全新的治疗方法,极具发展潜力。本文对BM—MSCs的分离培养、诱导因素、移植以及临床研究等方面进行了综述。     

骨髓间充质干细胞移植治疗心肌梗死的新技术

骨髓间充质干细胞移植是治疗心肌梗死的新途径之一,其技术和方法不断发展.诸如建立更好的大型活体实验动物模型;改进对植入细胞的标记追踪技术;进一步研究细胞植入的适宜方式和时间等.骨髓间充质干细胞移植和基因疗法相结合可能得到叠加的治疗效果.     

骨髓间充质干细胞移植治疗心肌梗死的研究进展

骨髓间充质干细胞是一种多能干细胞,在体外培养时,可以通过诱导使其分化为心肌细胞等。目前进行的动物实验和临床Ⅰ期实验表明骨髓间充质干细胞具有促进血管增生以及改善心肌梗死后心脏功能的作用,为心肌梗死的治疗提供了广阔前景。     

骨髓间充质干细胞移植治疗心肌梗死机制的研究进展

心肌梗死（myocardial infarction,MD是由于冠状动脉循环改变引起冠状血流和心肌需求之间不平衡而导致的心肌损害,是临床上一种严重的缺血性心脏病（ischemic heart isease,IHD）。梗死的心肌细胞逐渐被瘢痕组织取代,由于瘢痕组织缺乏弹性,难以满足心脏收舒功能的要求,     

兔骨髓间充质干细胞移植后移植细胞凋亡的实验研究

目的利用TUNEL法检测5-氮胞苷体外诱导骨髓间充质干细胞（MSCs）移植后的凋亡情况。方法5-氮胞苷体外诱导骨髓间充质干细胞MSCs向肌源性心肌细胞分化,通过免疫组化,鉴定诱导后的MSCs是否向类心肌细胞转化。建立兔心肌梗死模型,将细胞移植于心梗区域。移值2周后,利用TUNEL法检测植入细胞的凋亡率。结果移植2周后,可见DAPI标记带蓝色荧光的供体细胞核,分布比较广泛,形态呈椭圆形类似心肌细胞核,并与心肌纤维排列方向一致,证明移植细胞已存活。移值细胞表达troponinT,证明移植的MSCs分化为类心肌细胞。移植细胞均出现不同程度细胞凋亡。结论移植的MSCs细胞可在缺血的心肌组织存活,并分化为类心肌细胞,但移植细胞均出现不同程度凋亡。     

脂肪间充质干细胞移植治疗扩张型心肌病大鼠的研究

目的 脂肪间充质干细胞（ADMSCs）移植对扩张型心肌病(DCM)大鼠心肌损伤及心功能的影响。方法 80只健康Wistar大鼠腹腔注射阿霉素建立DCM大鼠模型，按随机数字表法分为治疗组和对照组，各35只（建模中死亡5只，建模后又处死5只）。将体外分离培养的ADMSCs移植入治疗组DCM大鼠，同时将以相同体积的IMEM培养基移植入对照组DCM大鼠。术后4周，处死动物留取心脏，于荧光显微镜下观察ADMSCs植入后存活及分化情况。于细胞移植术前、术后4周，将两组大鼠进行超声心动图、血流动力学检查，测定、比较心功能的指标。结果 ①注药4周后，根据留取大鼠心脏的大体形态、病理切片及心功能指标，提示DCM大鼠模型建立成功。②移植术后4周，于移植部位可见DAPI标记的ADMSCs，同时，免疫组织荧光染色发现部分DAPI阳性细胞，TnT染色也为阳性，且排列方向与心肌细胞一致。③移植术后4 周, 对照组与ADMSCs治疗组比较，左心室舒张末容积（LVEDV）及左心室收缩末容积（LVESV）明显减少(P<0.01)；左心室每搏量(SV)、心脏射血分数(EF)、左心室收缩压(LVSP)、左心室室内压最大上升/下降速率（±dp/dtmax）均明显增加(P<0.05,P<0.01)。结论 ADMSCs移植可在心肌内存活,并可分化为心肌细胞, 改善DCM大鼠的心脏功能。     

Effects of nitric oxide inhibition on basal forearm blood flow in patients with nonischemic chronic heart failure

Summary Increased peripheral vascular tone in patients with chronic heart failure (CHF) is an important factor which contributes to increased cardiac afterload and reduced exercise capacity, and consequent further deterioration in CHF. The role of endogenous nitric oxide (NO) in the regulation of basal vascular tone in CHF is controversial. This study has investigated (1) whether basal NO bioavailability is reduced in the peripheral vasculature of patients with nonischemic CHF in the absence of confounding factors influencing endothelial function, and (2) if a difference is found, what clinical characteristics are related to the decreased NO-dependent vasodilation. Basal forearm blood flow (FBF) of 12 patients with CHF and 14 healthy volunteers was measured before and after administration ofN ^G-monomethyl-l-arginine (l-NMMA) by venous occlusion plethysmography. Afterl-NMMA administration, basal FBF in both healthy subjects and patients with CHF decreased significantly, with the decrease in CHF patients being less than that in healthy volunteers (–0.7 ± 0.2 vs –1.5 ± 0.2ml/min per 100ml tissue,P < 0.01). When both groups were considered together, basal FBF was closely related to the decrease in FBF afterl-NMMA administration (r = –0.83.P < 0.001). When CHF patients were divided into two groups according to NYHA class, thel-NMMA-induced decrease in FBF in moderate CHF (NYHA III;n = 7) was significantly less than that in mild CHF (NYHA II;n = 5) (–0.36 ± 0.13 vs –1.16 ± 0.72ml/min per 100ml tissue,P < 0.05). In conclusion, basal bioavailability of NO in the peripheral vascular bed in nonischemic CHF is impaired, with an increase in basal vascular tone and with progression of this disorder. This suggests that impaired basal NO bioactivity may make an important contribution to the elevated peripheral vascular tone and expression of symptoms seen in CHF.     

西沙比利对大鼠胃粘膜血流影响的实验研究

目的本文研究了西沙比利对大鼠胃粘膜血流的影响,并进而探讨其可能的作用机制.方法32只Wistar大鼠随机分为对照组,西沙比利0.5mg/kg组,1mg/kg组和2mg/kg组,采用中性红分泌法和grees-reactin方法检测胃粘膜血流及一氧化氮含量.结果西沙比利1mg/kg组大鼠胃粘膜血流量为(0.7±0.13mL/min),显著高于空白对照组(0.45±0.18mL/min)和西沙比利0.5mg/kg组(0.4±0.24mL/min)(P＜0.50),且西沙比利1mg/kg组胃粘膜一氧化氮含量亦显著高于空白对照组(23.32±7.40μmol/L/mg vs16.93±3.87μmol/l/mg)和西沙比利0.5mg/kg组(16.76±1.06μmol/L/mg)(P＜0.05).西沙比利2mg/kg组胃粘膜血流量为(0.3±0.17mL/min),显著低于空白对照组(0.45±0.18mL/min)(P＜0.05),其一氧化氮含量(4.35±1.52μmol/L/mg)亦显著低于空白对照组(P＜0.05).结论西沙比利通过影响胃粘膜内一氧化氮含量从而改变胃粘膜血流,西沙比利1mg/kg对大鼠胃粘膜具有保护作用.     

丹参对重症急性胰腺炎大鼠腹腔器官血流的影响

目的:研究丹参对重症急性胰腺炎(SAP)大鼠腹腔器官血流,特别是胰腺血流的影响及其作用机制.方法:将大鼠随机分成丹参治疗组(SM)和重症急性胰腺炎组(SAP).各组分别有数只大鼠于术后12、24 h处死,观察血浆淀粉酶的变化.另设正常对照组.运用多普勒超声测定胰腺局部动脉(相当于胰头、体交界处)、门静脉血流、脾动脉及肠系膜上动脉血流.结果:丹参组12、24 h的血浆淀粉酶明显低于相同时点的SAP组(8091.2±1574.9 vs 15 142.8±2900.5,8312.5±981.1 vs 16 987.1±1584.6,P<0.011.丹参组和SAP组大鼠胰腺局部动脉,门静脉、脾动脉及肠系膜上动脉中的血流在术后12 h时与对照组相比明显下降(P<0.01).随胰腺炎的病程进展,其24 h局部血流相比12 h时的下降更趋严重.丹参组12、24 h大鼠胰腺局部动脉,门静脉、脾动脉和肠系膜上动脉的血流量与SAP组相同时点相比明显增加(12 h:0.49±0.04 vs 0.33±0.06,0.60±0.04 vs 0.39±0.08.0.53±0.04 vs 0.42±0.08:0.57±0.08 vs 0.42±0.06:24 h:0.38±0.04 vs 0.29±0.04,0.59±0.04 vs 0.41±0.01.0.54±0.06 vs 0.32±0.02.0.49±0.05 vs 0.38±0.04,P<0.011.结论:丹参能促使SAP大鼠胰腺血流量增加     

Intrapulmonary bronchial blood flow of rats as studied by the microsphere method

Summary The intrapulmonary bronchial blood flow of the left lung (systemic arterial blood flow to the left lung via the bronchial artery) was determined in 45 anesthetized and artificially ventilated male Wistar rats, weighting 263±5 g (mean ± SEM). The microsphere method was employed and designed so that recirculating microspheres across the peripheral arteriovenous anastomoses were prevented from lodging in the left lung, and disturbances of the isovolemic state of the animals became minimal. Under normal conditions with a mean arteiral pressure of 115±2 mmHg (n=40), the bronchial blood flow of the left lung was found to be 0.307±0.033 ml/min on average, and amounted to 0.52±0.06% of the cardiac output. The flow (ml/min) normalized per kg body weight, 100 g wet lung, or 100 g dry lung was 1.14±0.12, 76±8, or 368±39, respectively. The total intrapulmonary bronchial blood flow of the left and right lungs could be estimated by multiplying the intrapulmonary bronchial flow of the left lung by the weight ratio (total: left) of 2.9. The variability of the flow data was small, as confirmed in a study with simultaneous injection of two differently radiolabeled microspheres. The reproducibility of duplicate measurements was excellent.     

氟桂利嗪对高血压大鼠脑血流自动调节功能的保护作用

目的探讨氟桂利嗪对高血压大鼠脑血流自动调节下限(LLCA)改变的治疗作用。 方法建立肾血管性高血压大鼠模型220只,将其随机分为治疗组(156只)和对照组(64只)。 治疗组再分为8个亚组,造模后按顺序每隔2周开始插胃管喂食氟桂利嗪治疗(0．2 mg/kg,1次／ d)。然后每隔2周或4周,分别从各亚组中抽取6只大鼠,利用临界关闭压法测定LLCA。对照组 从造模术后2周开始,每隔2周抽取8只大鼠测定LLCA。 结果造模术后即刻开始治疗组大鼠 第6、10周末的LLCA,分别为(71±4)mmHg和(72±26)mmHg,对照组大鼠的LLCA分别为 (97±18)mmHg和(114±10)mmHg,(P均<0．05)。第2、4周开始治疗组大鼠第8周末的LLCA分别为(86±9)mmHg和(67±12)mmHg,对照组为(100±11)mmHg,(P均<0．05)。第6 周开始治疗组,第10周末LLCA明显低于对照组(P<0．05)。第8-14周开始治疗组大鼠的LLCA和对照组比较,差异无显著性。治疗组大鼠LLCA的改变与收缩压呈显著正相关(r=0．872, P<0．05)。 结论 在高血压早期,氟桂利嗪可一定程度地阻止高血压大鼠的LLCA上移。     

Effects of the carbonic anhydrase inhibitor acetazolamide on splanchnic blood flow in anaesthetized rats

The aim of the present study was to evaluate whether inhibition of the enzyme carbonic anhydrase with acetazolamide interfered with pancreatic islet and whole splanchnic blood perfusion in rats. Carbonic anhydrase is present both in the endocrine cells and, in particular, the endothelium of the pancreatic islet. Thiobutabarbital-anaesthetized, male Sprague-Dawley rats were used in all experiments, and acetazolamide (50 mg/kg body weight) was given to untreated control rats or rats pretreated with glucose, i.e. to normoglycaemic and hyperglycaemic animals. No acetazolamide-induced effects on blood glucose or serum insulin concentrations, mean arterial blood pressure, whole pancreatic or islet blood flow were seen in any of the animals. There were no effects on duodenal or colonic blood flow recorded in the control rats, whereas an increase in duodenal blood flow (P<0.02) was observed in the hyperglycaemic animals. A tendency to an increase was seen in colonic blood flow in hyperglycaemic animals, although this was not statistically significant (P=0.069). Inhibition of carbonic anhydrase seems to induce only minor effects on pancreatic blood flow, while duodenal blood flow is slightly enhanced in hyperglycaemic animals. Received: 25 May 1998 / Accepted in revised form: 23 October 1998     

Extra-ascending aortic versus intra-descending aortic balloon counterpulsation-effect on coronary artery blood flow

BACKGROUND: Diastolic counterpulsation has been used to provide circulatory augmentation for chronic heart failure or for short-term cardiac support. Recently an extra-aortic balloon (EAB) counterpulsation device has been proposed. AIM: To compare the circulatory effects of counterpulsation using the EAB or an intra-aortic balloon (IAB) in the acute pig model. METHODS: In six anaesthetized great white pigs (paced at 100 bpm), ECG, arterial and central venous pressures, flow in the coronary circulation and descending thoracic aorta were measured. Baseline data was collected, then with the EAB or an IAB fitted using 1:1 and 1:2 counterpulsation modes. Baseline data was compared to EAB and IAB data in 1:1 mode. Assisted beat data compared to unassisted beat data was also analysed in 1:2 mode. RESULTS: Both devices augmented peak diastolic arterial pressure, and decreased afterload. EAB counterpulsation increased diastolic coronary flow in both the 1:1 mode by 69% (p < 0.05) and in the 1:2 mode by 63% (assisted versus unassisted beat, p < 0.05). The IAB significantly increased diastolic coronary flow only in the 1:2 mode by 28% (p < 0.01). Both devices augmented total coronary flow and some augmentation of aortic flow was observed. CONCLUSION: The circulatory effect of the EAB and IAB counterpulsation were comparable. This suggests the EAB could be used as a non-blood contacting heart assist device in patients suffering moderate-severe heart failure.     

Laser Doppler velocimetry and the measurement of colostomy blood flow

Early colostomy closure leads to a high rate of fecal fistula formation which may be due to a poor blood supply. Laser Doppler flowmetry is a new method of measuring colonic blood flow. Blood flow in 17 colostomies has been measured at one week, median flux 28 units (range, 13 to 43) and in 12 colostomies more than eight weeks after formation, median flux 46 units (range, 35–56;P<0.002). Nine of the “mature” colostomies have been closed without a fecal fistula or other signs of anastomotic failure. Serial readings of colostomy blood flow were made at weekly intervals in another ten stomas over a period of two months. Blood flow increased over this time from a median of 19 units (range, 17 to 22) at one week to a median of 44 units (range, 39 to 48;P<0.002) at eight weeks. Laser Doppler flowmetry is a simple, noninvasive method of measuring colostomy blood flow and the findings support a clinical policy for delayed colostomy closure.     

NI—Ti网状食管支架术后局部血流量变化分析

目的 研究实验犬食管支架术后0．5、24小时局部粘膜血流量的变化。方法 选择成年、健康犬12只,分别置入NI－Ti网状自扩张食管支架,采用多普勒血流仪检测支架术后0．5、24小时局部粘膜血流量的变化,与正常食管粘膜进行比较。结果 支架术后0．5、24小时食管局部粘膜血流量较正常食管均明显减少。结论 支架置入可导致食管局部粘膜血流量明显降低,从而促进粘膜的损害,说明支架对食管壁具有明显的损伤作用。