Objective To investigate the effect of mesenteric lymphatic duct liagtion and glutamine enteral nutrition on intestine and distant organs in intestinal ischemia/reperfusion injury. Methods Forty male SD rats undergoing gastrostomy were randomly assigned into 5 groups (n=8): sham operation group, normal enteral nutrition group, normal enteral nutrition+lymphatic duct ligation group, glutamine group and glutamine+lymphatic duct ligation group. Sham operation group only received laparotomy after 7 days of full diet, the other four groups were subjected to 60 min of intestinal ischemia after 7 days of enteral nutrition, and the two lymphatic duct ligation groups were plus mesenteric lymphatic duct ligation. The original nutrition continued 3 days after reperfusion. Intestinal permeability was detected on day 1 before reperfusion, day 1 and 3 after reperfusion. Intestinal morphology was observed, endotoxin, D-lactate and diamine oxidase levels in serum, and apoptotic index in lung tissue were detected on day 3 after reperfusion. Results The intestinal permeability in each group was significantly increased on day 1 after reperfusion (Plt;0.05), and which in normal enteral nutrition+lymphatic duct ligation group and glutamine+lymphatic duct ligation group were significantly decreased on day 3 after reperfusion (Plt;0.05). The mucosal thickness and villus height of ileum and mucosal thickness of jejunium in glutamine+lymphatic duct ligation group were significantly higher than those in other groups (Plt;0.05), and villus height of ileum in glutamine group was higher than that in normal enteral nutrition group (Plt;0.05); those morphology indexes in normal enteral nutrition+lymphatic duct ligation group were higher than those in normal enteral nutrition group, but there was no statistical signification (Pgt;0.05). Apoptosis index of lung tissue in lymphatic duct ligation groups was significant lower than that in no-ligation groups (Plt;0.05). Levels of endotoxin, D-lactate, and diamine oxidase in lymphatic duct ligation groups had downward trends compared with no-ligation groups, but there was no statistical signification (Pgt;0.05). Conclusions Intestinal ischemia/reperfusion injury of rats can cause intestinal permeability increase, bacterial endotoxin translocation and systemic inflammatory response. Mesenteric lymphatic duct ligation and glutamine enteral nutrition intervention can weak lung tissue damage, increase thickness of intestinal mucosa, maintain intestinal barrier function, reduce endotoxin translocation and attenuate systemic inflammatory response. Enteral nutrition with glutamine was better than normal enteral nutrition.
Diabetic macular ischemia (DMI) is one of the manifestation of diabetic retinopathy (DR). It could be associated with diabetic macular edema (DME), which may affect the vision of DR patients. FFA is the gold standard for the diagnosis of DMI, but with the advent of OCT angiography, a more convenient and diversified method for the evaluation of DMI has been developed, which makes more and more researchers start to study DMI. Intravitreal injection of anti-VEGF has become the preferred treatment for DME. When treating with DME patients, ophthalmologists usually avoid DMI patients. But if intravitreal anti-VEGF should be the contradiction of DME is still unclear. To provide references to the research, this article summarized the risk factors, assessment methods and influence of DMI. This article also analyzed the existing studies, aiming to offer evidences to a more reasonable and effective treatment decision for DME individual.
Objective To summarize the research progress of gene-based therapeutic angiogenesis in lower limb ischemia, so as to provide a new method for non-invasive treatment of lower limb ischemia. Method The literatures on studies of gene-based therapeutic angiogenesis in lower limb ischemia in recent years were read and reviewed. Results The incidence of peripheral arterial disease had been increasing annually. How to effectively reduce the amputation rate and mortality rate of patients with critical limb ischemia was still a clinical problem that needs to be solved urgently. A large number of basic and clinical studies had shown that gene-based therapeutic angiogenesis could effectively induce angiogenesis and collateral circulation in ischemic tissue of lower limb, leading to the significant improvements of blood perfusion in ischemic areas. Additionally, the construction of many kinds of new non-viral gene delivery vectors could also improve the safety and effectiveness of gene therapy to a certain extent. Conclusion Although promising therapeutic effect of gene-based therapeutic angiogenesis brings new ideas and strategies for the treatment of lower limb ischemia, issues still exist that have not been solved.
Objective To explore the effective autologous bone marrow stem cell dosage for treatment of severe lower limb ischemia. Methods From December 2003 to December 2004, 22 cases of bilateral lower limb ischemia were treated with autologous bone morrow cell transplantation. All the patients were randomly divided into two groups according to ischemia degree. In group A(severe ischemia side), the amount of transplanted autologous bone marrow cells was more than 1×108, and ingroup B(mild ischemia side), the amount was less than 1×105. A series of subjective indexes, such as improvement of pain, cold sensation and numbness, and objective indexes, such as increase of ankle/brachial index (ABI) and transcutaneous oxygen pressure (TcPO2), angiography, amputation rate, and improvement of foot wound healing were used to evaluate the effect of autologous bone marrow stem cells implantation. Results The rates of pain relief were 90.0% in group A and 16.7% in group B (Plt;0.01); the rates of cold sensation relief were 90.5% in group A and 5.3% in group B（Plt;0.01）;the improvement of numbness was 62.5% in group A and 9.1% in group B（Plt;0.01）. Increase of ABI was 31.8% and 0 in groups A and B respectively（Plt;0.01） at 4 weeks after implantation. Increase of TcPO2was 94.4% and 11.1% in groups A and B respectively（Plt;0.01） at 4 weeks after implantation. Twelve cases of angiography showed rich new collateral vessels in 100% of the limbs in group A while no remarkable new collateral vessel in group B. The amputation rates were 4.5% in group A and 27.3% in group B（Plt;0.05） at 4 weeks after implantation. The rate of improvement of foot wound healing was 75% in group A and there was no changein wound healing in group B after 4 weeks of implantation. Conclusion The effectiveness of autologous bone marrow stem cell implantation depends on the number of implanted stem cells. Effectiveness is expected in most patients if the implanted stem cell is more than 1×108, whereas there would be little effect if the cell number is less than 1×105.
Objective To systematically evaluate the influence of alcohol intervention on the outcome of rats and mice with ischemic stroke. Methods Databases including PubMed, EMbase, BIOSIS and CNKI were electronically searched from establishment dates of databases to June 2012 to retrieve animal experiments on the influence of alcohol intervention on the outcome of rats and mice with ischemic stroke. The relevant studies were identified according to the predefined inclusion and exclusion criteria, the data were extracted, and the quality was evaluated. Then meta-analysis was performed using RevMan 5.1 software. Results Eight studies were included. The results of meta-analysis showed that no significant difference was found between the alcohol intervention group and the control group (MD=−6.98%, 95%CI −20.38% to 6.43%, P=0.31). However, compared with the control group, low dose of acute alcohol intervention (less than 2 g/kg) improved the prognosis of ischemic stroke with a significant difference (MD=−22.83%, 95%CI −38.77% to −6.89%, P=0.005), and highly-concentrated of chronic alcohol intervention worsened the cerebral ischemic damage of rats and mice with a significant difference (MD=24.06%, 95%CI 10.54% to 37.58%, P=0.000 5). Conclusion Low dose of acute alcohol intervention (less than 2 g/kg) could improve the prognosis of rats and mice with ischemic stroke which has the potential neuro-protective effects. However, highly-concentrated chronic alcohol intervention could worsen the cerebral ischemic damage. Due to the limitations of the included studies such as publication bias, the influence of alcohol intervention on the outcome of rats and mice with ischemic stroke could be overestimated.
Objective To investigate the expression of hypoxia inducible factor 1α (HIF-1α) protein and the activation of phosphoinositid 3-kinase/Akt (PI3K/Akt) signal ing pathway in neurons under hypoxia ischemia condition,and to elucidate the role of PI3K/Akt on HIF-1α regulation in the developing neurons after hypoxia ischemia brain damage(HIBD). Methods Fifty-six SD rats aged 10 days were randomly divided into normal control group (n=12), sham operationgroup (n=12), experimental group (n=24), wortmannin treated group (n=4) and DMSO/PBS treated group (n=4). In theexperimental group, the rats were anesthetized with ethylether. The right common carotid artery was exposed and l igated. Then, they were exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2.5 hours. In the sham control group, the right common carotid artery was exposed but was not l igated or exposed hypoxia. In the normal control group, the rats recevied no further processing. For wortmannin treated group and DMSO/PBS treated group, the rats received intraventricular injection of wortmannin or DMSO/PBS 30 minutes before hypoxia ischemia. The brain tissues were harvested from the rats in the normal control, sham operation and experimental groups at 4, 8 and 24 hours after hypoxia ischemia, but in the wortmannin and DMSO/PBS treated groups only at 4 hours. The HIF-1α protein expression and Akt protein expression were detected with immunohistochemistry method. HIF-1α, Akt and p-Akt protein expression were measured by Western blot analysis. Results In the experimental group, the HIF-1α expression was significantly increased at 4 hours after operation, reached the peak level at 8 hours, and began to decrease at 24 hours. The p-Akt protein was significantly increased at 4 hours, and began to decrease at 8 hours. However, the expression levels of HIF-1α and p-Akt protein in the normal control group were extremely low at each time point. So, the expression levels of HIF-1α in the experimental group was significantly higher than that in the normal control groups (P lt; 0.01), the expression of p-Akt protein in the experimental group at 4 and 8 hours was significant higher than that in the normal control group (P lt; 0.05). The change of Akt protein in the experimental group was not time-dependent, and no significant difference was evident when compared with that of the normal control group (P gt; 0.05). Using wortmannin, the PI3K/Akt specific inhibitor, HIF-1α protein expression was significantly decreased when compared with the DMSO/PBS treated group and experimental group (P lt; 0.01). Conclusion These results suggested that the HIBD of neonatal rats may activate PI3K/Akt signal ing pathway and further induce the expression of HIF-1α, indicating PI3K/Akt signal ing pathway and HIF-1α could be a potential target for treatment of neonatal HIBD.
ObjectiveTo explore the relationship between the oxygen partial pressure of mice hindlimb muscles with normal blood supply or ischemia and expression of HIF-1αprotein, and to provide a theoretical basis for the study of angiogenesis in vitro hypoxia. MethodsMice hind limb ischemia model were established, tissue oxygen tension of gastrocnemius muscle and bone marrow were measured by micro electrode at different time points of ischemia (24 hours, 1 week, 2 weeks, 3 weeks, and unoperated as control). Protein level of hypoxia inducible factor-1αand histological examination were performed on gastrocnemius muscle as well. ResultsThe oxygen tension baselines of gastrocnemius muscle and femoral bone marrow was (47.78±4.37) mm Hg and (21±3.40) mm Hg, respectively. Muscle oxygen tension decreased significantly at all time points after modeling (P < 0.05), and reached lowest level in 1 week of ischemia. The inflammatory reaction was most serious and HIF-1αprotein reached highest level at the same time point. With the extension of ischemic time, the tissue oxygen tension recovered while HIF-1αlevel was down-regulated, however, There was no statistical correlation(r=-0.86, P > 0.05). Oxygen tension in bone marrow didn't show any significant change at all time points. ConclusionsThe expression level of HIF-1αprotein in ischemic tissue can reflect the degree of ischemic limb. The concept that physiological oxygen level differs in different tissue is highlighted, and may provide basis for ex vivo hypoxic research.
Objective To summarize the experience of emergency coronary artery bypass grafting(CABG) on serious myocardium ischemia in early post CABG. Methods Between 1998 and 2002, emergency redo CABG was performed in 13 patients with serious early post operative myocardium ischemia. The causes included vein graft embolize(4 cases),uncompleted revascularize(3 cases), graft spasm(1 case) and anastomose stenosis or occlusion (5 cases). The grafts was 1 3(1.8±0.9) during redo CABG. Results There were 6 deaths, the mortality was 46%. The mean follow up was 31 months. There was no recurrence of angina. NYHA function was Ⅰ Ⅱ. Conclusion Emergency CABG is an important method in saving the patients with severe myocardium ischemia in early post CABG. The perioperative prevention and early treatment should be emphasized.
This study aims to investigate the effect of lung ischemia reperfusion injury (LIRI) on expression of transient receptor potential vanilloid 1 (TRPV1) in the lung and brainstem of rats. Sixteen adult male Sprague Dawley rats weighing 250-320 g were randomly divided into Sham group and ischemia reperfusion group (IR group). Before ischemia, 0.5 hour and 4 hours after the reperfusion, respectively, arterial partial pressure of oxygen (PaO2) and arterial-alveolar oxygen pressure gradient (A-aDO2) were recorded and calculated, respectively. Left lung tissues and the brainstems were obtained at the end of the experiment. Lung tissue malondialdehyde (MDA), myeloperoxidase (MPO) activities, calcitonin gene related peptide (CGRP) and substance P (SP) levels were assessed. The mRNA and protein expressions of TRPV1 in the lung and brainstem were measured by qRT-PCR and Western blot. Compared with in the Sham group, rats in the IR group had a poorer blood gas exchange (P<0.05) and the MPO activity and MDA level of lung tissues in the IR group were significantly higher than those in the Sham group (P<0.05). CGRP level in the IR group increased remarkably (P<0.05), while SP level did not differ statistically between the two groups (P>0.05). The mRNA and protein expressions of TRPV1 in the lung tissue were upregulated in the IR group (P<0.05), but there were no differences of those in the brainstem between the two groups (P>0.05). The results suggest that LIRI could upregulate the expressions of TRPV1 and evoke CGRP release in the lung.
Objective To investigate the efficiency and safety of autologous peripheral blood stem cell transplantation （ABSCT） in treatment for thromboangiitis obliterans. Methods Fifty patients （62 affected limbs） with thromboangiitis obliterans were treated by ABSCT. A series of subjective indexes including improvement of pain and cold sensation and objective indexes including intermittent claudication distance， ankle brachial index （ABI）， skin temperature， and improvement of foot skin ulcer were evaluated. Results Due to necrosis in middle and lower part of leg， 4 of 50 patients （4 lower limbs） were taken extremity amputation on 3 weeks after ABSCT， 46 patients kept their legs successfully. On 1 month after ABSCT， the legs pain and cold sensation of 46 patients （58 affected limbs） vanished， and the score of feet pain and cold sensation after ABSCT were better than those before ABSCT （P＜0.05）. The intermittent claudication distance， skin temperature， and ABI of 46 patients with kepting their legs on 3 months after ABSCT significantly increased as compared with before ABSCT 〔intermittent claudication distance：（80.38±45.53） m versus （330.56±142.31） m；skin temperature：（26.50±0.46） ℃ versus （31.49±0.45） ℃；ABI：0.41±0.02 versus 0.71±0.05〕， the differences were statistically significant（P＜0.05）. Six months after ABSCT， different degree neonatal lateral vessels were found in 58 affected limbs of 46 patients by lower extremity arteriography. The complications were not found in all the patients by laboratory or CT detection， such as malignant tumors， retinal hyperplasia， aneurysm and so on. After ABSCT， 40 patients were followed up for 9 to 36 months （mean 22.5months）， the symptom had improved. Due to leg pain aggravated after 6 months， score of pain feelings was 4 in 6 patients and with toe ulcers， who had ABSCT again. Eighteen months after transplantation， the patients had only debilitation of lower extremity. The pain feeling was improved （score of pain feeling was 1）. The toe ulcer was healed and no angiosclerotic myasthenia happened. Conclusions ABSCT is a simple， safe， and effective method， especially in treatment for patients with severe lower limb ischemia who is no arterial reconstruction is feasible. It could improve the quality of life of patients and might be avoided amputation of lower extremity or foot.