黄芪注射液对压力超负荷大鼠心肾功能的保护作用

目的:观察黄芪注射液对腹主动脉缩窄致慢性压力超负荷大鼠心肾功能的保护作用及机制。方法:雄性SD大鼠70只,随机选取10只大鼠为假手术组,其余60只制作腹主动脉缩窄模型,随机分为模型组,黄芪组和阳性对照厄贝沙坦组(n=20)。各组大鼠在术后24h开始给药,黄芪组每天腹腔注射黄芪注射液2ml(2g.kg-1.d-1),假手术组、模型组和厄贝沙坦组每天腹腔内注射2ml生理盐水,其中厄贝沙坦组将厄贝沙坦片溶于饮水中(50mg.kg-1.d-1)。连续给药12周后,存活大鼠行血流动力学测定心功能,取血测定肾功能指标血尿素氮(BUN)、肌酐(Scr),留取心脏及肾脏标本,HE及Masson染色观察心脏及肾脏病理组织学变化。结果:与模型组相比,黄芪组和厄贝沙坦组大鼠心功能明显好转,其中LVSP,±dP/dtmax显著升高(P<0.05),而LVDP显著降低(P<0.05);血尿素氮(BUN)、肌酐(Scr)显著降低(P<0.05);心肌组织水肿减轻;肾小管空泡变性、坏死明显减少,结构基本完整,间质胶原沉积减少,MMP-2和MMP-9的表达降低。结论:黄芪注射液可改善心力衰竭大鼠的心、肾功能及心、肾组织结构,拮抗肾间质纤维化。     

N-乙酰-L半胱氨酸对大鼠糖尿病肾病的保护作用

氧化应激是糖尿病肾病(DN)发生、发展的重要环节之一,抗氧化剂能阻止或延缓DN发生、发展.本实验研究抗氧化剂N-乙酰-L半胱氨酸(NAC)对DN保护作用的机制. 一、材料和方法 1.模型制备及分组:30只大鼠随机分为正常对照组、DN组、NAC组,每组10只.STZ腹腔注射造模成功后,NAC组大鼠每日予NAC 75 mg灌胃,8周后处死动物,留取肾皮质待测.     

三甲氧苄嗪对大鼠离体心脏再灌注损伤的保护作用

目的　探讨三甲氧苄嗪增补于心脏停搏液中对离体鼠心再灌注损伤的保护作用。　方法　将 2 4只Wistar大鼠随机分为实验组和对照组。离体鼠心在改良的 L angendorff- Neely灌注模型上 30分钟预灌注 ,12 0分钟停搏 ,30分钟再灌注。缺血前和再灌注期间测定血流动力学指标、心肌酶中血清肌酸激酶 (CK)、血清乳酸脱氢酶(L DH)、心肌超氧化物歧化酶 (SOD)、过氧化脂质 (L PO)含量、心肌三磷酸腺苷 (ATP)水平。电子显微镜观察心肌超微结构。　结果　再灌注后 ,实验组心功能、心肌超微结构的改善明显优于对照组 ,CK、L DH和 L PO含量显著低于对照组 (P<0 .0 1) ,SOD含量和心肌 ATP水平显著高于对照组 (P<0 .0 1)。　结论　三甲氧苄嗪增补于心脏停搏液中可显著减轻心肌缺血 -再灌注损伤 ,具有良好的心肌保护作用。     

N-乙酰半胱氨酸对糖尿病肾病大鼠足细胞的保护作用

目的：探讨N-乙酰半胱氨酸（NAC）对糖尿病肾病（DN）大鼠足细胞的保护作用。方法：制备DN大鼠模型,将动物随机分为正常对照组、DN组和NAC组。8周后观察尿蛋白排泄量,免疫荧光方法和Western blotting检测肾皮质nephrin和podocin蛋白表达,透射电镜检测足细胞超微结构变化。结果：（1）与正常对照组比较,DN组和NAC组尿白蛋白排泄率增多（P〈0.01）,nephrin和podocin蛋白表达减少（P〈0.01或P〈0.05）和肾脏病理病变明显;（2）与DN组比较,NAC组尿蛋白排泄减少（P〈0.01）,nephrin和podocin蛋白表达较高（P〈0.01或P〈0.05）和足细胞的病变较轻。结论：NAC对DN大鼠肾脏保护作用,其部分机制与上调nephrin和podocin蛋白表达及改善足细胞病变有关。     

Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation

We investigated the effects of the antioxidant N-acetylcysteine (NAC) on early outcomes of deceased donor renal transplantation. Between April 2005 and June 2008, adult primary graft recipients of deceased renal donors were assigned to treatment (n = 38) or control (n = 36) groups and evaluated for 90 days and one year after renal transplantation. The treatment group received NAC orally (600 mg twice daily) from day 0 to 7 postoperatively. Renal function was determined by serum creatinine, MDRD and Cockcroft-Gault estimated GFR (eGFR), delayed graft function (DGF) and dialysis free Kaplan-Meier estimate curve. Serum levels of thiobarbituric acid reactive substances (TBARS), were employed as markers of oxidative stress. The NAC group displayed a lower mean serum creatinine during the first 90 days (P = .026) and at 1 year after transplantation (P = .005). Furthermore, the NAC group showed a higher mean eGFR throughout the first 90 days and at 1 year. DGF was lower among the NAC group (P = .017) and these recipients required fewer days of dialysis (P = .012). Oxidative stress was significantly attenuated with NAC (P < .001). Our results suggested that NAC enhanced early outcomes of deceased donor renal transplantation by attenuating oxidative stress.     

细胞内液型胶体液HBS对离体心脏的长期保存作用

探讨自制的含组氨酸、Ｂｉｍａｋａｌｉｍ的细胞内产体液对离体心脏的保存作用。方法：”健康性ＳＤ大鼠１６只，体重２４０－２６０ｇ。随机均分为两组，采用微量灌注技术，分别用ＨＢＳ和托马斯停搏液４℃保存离体鼠心２４小时，再灌注６０分钟进行比较研究。     

Protective effect of N-acetylcysteine on renal ischemia/reperfusion injury in the rat

BACKGROUND: Oxygen free radicals are important components involved in the pathophysiological tissue alterations observed during ischemia/reperfusion (I/R). METHODS: The protective effect of N-acetylcysteine (NAC) against the damage inflicted by reactive oxygen species during renal I/R was investigated in Wistar Albino rats using biochemical parameters. Animals were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by lh of reperfusion. N-acetylcysteine (150 mg/kg, i.p.) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. For biochemical analysis, the lipid peroxidation product malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and protein oxidation (PO) were tested. Serum creatinine and BUN concentrations were measured for the evaluation of renal function. RESULTS: I/R induced nephrotoxicity, as evidenced by increases in BUN and creatinine, was reversed by NAC. The decrease in GSH and increases in MDA, MPO and PO induced by I/R indicated that renal injury involves free radical formation. CONCLUSIONS: Since NAC reversed these oxidant responses, and protected rat renal proximal tubules from in vitro simulated reperfusion injury, it seems that NAC protects kidney tissue against oxidative damage.     

阿魏酸钠对糖尿病肾病的保护作用及机制

目的：观察阿魏酸钠对糖尿病肾病伴高脂血症患者血脂、内皮素、一氧化氮、24h尿蛋白的影响。方法：将60例糖尿病肾病伴高脂血症患者随机分为治疗组（30例）和对照组（30例）,两组基础治疗相同,治疗组在对照组基础治疗上加用阿魏酸钠,治疗4周后观察两组患者血脂、内皮素、一氧化氮、24h尿蛋白及临床症状的变化。结果：与对照组比较,治疗组在降低总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、内皮素（endothelin,ET）、24h尿蛋白和升高一氧化氮（nitric oxide,NO）方面疗效更为显著,两组升高高密度脂蛋白胆固醇（HDL-C）的疗效相似。结论：阿魏酸钠可有效调节糖尿病肾病伴高脂血症患者血脂水平,改善内皮功能,降低尿蛋白,对糖尿病肾病有保护作用。     

Changes in the Organ Procurement System in South Korea: Effects on Brain-Dead Donor Numbers

In Korea, the Organ Transplantation Act came into effect in 2000, establishing the Korean Network for Organ Sharing (KONOS) with centralized authority for organ procurement as well as for approval of donors and recipients to ensure fair organ allocation. However, the number of brain-dead donors decreased sharply, and the organ allocation system proved inefficient. The government revised the Organ Transplantation Act in August 2002, introducing an incentive system. If a transplantation hospital formed a Committee for Brain Death Evaluation and a Hospital Organ Procurement Organization, it could receive a kidney from a brain dead-donor as an incentive to foster organ procurement regardless of the KONOS wait list. The government also launched a pilot brain-dead donor registry program to strengthen Hospital Organ Procurement Organization activity. If local hospitals collaborated with specialized hospitals in organ procurement, local hospitals obtained financial incentives. But because the organ shortage problem has not been resolved, the government has proposed four initiatives: first, broadening the incentive system, which makes it possible to give each specialized hospital a choice of one of eight organs from each donor as an incentive; second, development of an Independent Organ Procurement Organization; third introduction of an opt-out system; and last, improvement of the Committee for Brain Death Evaluation system. It is uncertain which initiatives will be adopted, but changes in organ procurement systems are nonetheless considered a key to solve the organ shortage problem in Korea.     

N-乙酰半胱氨酸对大鼠辐射损伤相关肠屏障功能障碍的防护作用

目的探讨N-乙酰半胱氨酸（NAC）对大鼠小肠辐射损伤相关肠屏障功能障碍的防护作用及其作用机制。方法24只雄性SD大鼠随机分为3组,单纯照射组（8只）仅接受10Gyx线单次腹部照射：NAC治疗组（8只）予以10GyX线单次腹部照射并NAC（300mg／kg）腹腔注射7d（照射前4d开始给药,照射后3d停止给药）;正常对照组（8只）予以10％葡萄糖腹腔注射,注射时间同治疗组。照射后3d处死大鼠,取血桨、末端回肠、肝、脾及肠系膜淋巴结标本。光镜下观察并计算单位面积肠片上的肠腺存活率和绒毛数．测定血中D-乳酸、内毒素含量及二胺氧化酶（DAO）活性,检测小肠黏膜组织中一氧化氮（NO）水平,进行细菌培养以测定细菌易位率。结果辐射照射后,NAC治疗组大鼠肠腺存活率为（76．84±4．82）％,绒毛数量为（8．56±0．68）个／mm;与单纯照射组[（49．64±5．48）％和（4．02±0．54）个／mm]比较。差异有统计学意义（均P〈0．01）。两组大鼠小肠黏膜组织中NO含量分别为（0．48±0．12）μmol／g和（0．88±O．16）μmol／g,差异有统计学意义（P〈0．01）。NAC治疗组大鼠血浆D-乳酸含量、DAO活性、内毒素水平及肠道细胞易位率与单纯照射组比较,差异均有统计学意义（P〈0．05或P〈0．01）。结论NAC对辐射损伤相关肠屏障功能障碍具有防护作用．可能与其抑制炎性介质NO的产生有关。     

Effects of N-acetylcysteine on radiocontrast nephropathy in rats

OBJECTIVE: N-acetylcysteine (NAC) has yielded some promising results recently in the prevention of radiocontrast nephropathy (RCN). In this study, the structural and functional effects of NAC on RCN were analyzed. MATERIAL AND METHODS: Twenty-eight Wistar rats were randomized into four groups, as follows: Group 1, controls; Group 2, contrast; Group 3, contrast+NAC; and Group 4, NAC. All rats were deprived of water for 24 h and then contrast medium (ioxoglate; 10 ml/kg) was administered to Groups 2 and 3. NAC (50 mg/kg) was introduced enterally to Groups 3 and 4 at a dose of 50 mg/kg in 0.5 ml of distilled water, in four sequential doses 12h apart, starting after 12?h of water deprivation. After 4 days, rats were sacrificed. Creatinine clearance was calculated. The malondialdehyde (MDA) level was quantified in tissue samples. Slides stained with hematoxylin-eosin and periodic acid-Schiff were examined by means of light microscopy. Each tubular cross-section from all images was scored as either mild (preserved brush border, no necrosis), moderate (loss of brush border, no necrosis) or severe (loss of brush border accompanied by necrosis) and the frequencies of these lesion severities were compared. RESULTS: Mean baseline serum creatinine levels and creatinine clearances were similar in all groups. Mean serum creatinine level increased significantly only in Group 2 (0.6+/-0.1 vs 0.7+/-0.2 mg/dl; p<0.05). Tissue MDA levels were similar in all groups. Moderate (13.8%+/-1.5% vs 42%+/-1.4%; p<0.05) and severe (0% vs 40%+/-2.1%; p<0.05) lesions were significantly more frequent in Group 2 compared to Group 1. The frequency of severe lesions in Group 3 was found to be halved compared to that in Group 1 (40%+/-2.1% vs 20.2%+/-0.86%; p<0.05). CONCLUSION: NAC protects the kidneys following exposure to contrast medium as it decreased the severity of tubular lesions in rats.     

氨基酸对未成熟心肌保护作用的实验研究

研究天门冬氨酸或（和）谷氨酸强化血停搏液对未成熟心肌的保护效果。将２４只出生３～４周新西兰幼兔随机均分成４组：Ｉ组为冷血停搏液组，Ｉ组天门冬氨酸（２０ｍｍｏｌ／Ｌ）强化组，ＩＩ组谷氨酸（２０ｍｍｏｌ／Ｌ）强化组，ＩＶ组谷氨酸加天门冬氨酸（各２０ｍｍｏｌ／Ｌ）强化组。结果表明，心功能指标心输出量（ＣＯ）恢复百分率ＩＶ组、Ｉ组明显少于Ｉ组（Ｐ＜０．０１）；左室收缩压（ＬＶＳＰ）恢复百分率Ｉ、ＩＩ、ＩＶ组明显少于Ｉ组（Ｐ＜０．０１）；左室舒张压（ＬＶＤＰ）及左室压力微分（ｄｐ／ｄｔ）恢复百分率Ｉ、ＩＩ、ＩＶ组优于Ｉ组（Ｐ＜０．０５）。乳酸脱氢酶（ＬＤＨ）和磷酸肌酶（ＣＫ）漏出量（Ｕ／Ｌ）中，ＬＤＨ漏出量Ｉ组优于Ｉ组（Ｐ＜０．０５），ＩＩ、ＩＶ组明显优于Ｉ组（Ｐ＜０．０１）；ＣＫ漏出量ＩＩ、ＩＶ组明显优于Ｉ组（Ｐ＜０．０１）。Ｉ、ＩＩ、ＩＶ组心肌含水量（％）明显优于Ｉ组（Ｐ＜０．０１）。Ｉ、ＩＩ、ＩＶ组心肌结构保护明显优于Ｉ组。结论：谷氨酸或（和）天门冬氨酸强化血停搏液能明显增强对未成熟心肌的保护作用。氨基酸强化组间之所以差别不显著可能与模型有关     

Evaluation of the Suitability of Miniature Pigs as an Animal Model of Juvenile Osteochondritis Dissecans

Juvenile osteochondritis dissecans (JOCD) is a developmental disease characterized by formation of intra‐articular (osteo)chondral flaps or fragments. Evidence‐based treatment guidelines for JOCD are currently lacking. An animal model would facilitate study of JOCD and evaluation of diagnostic and treatment approaches. The purpose of this study was to assess the suitability of miniature pigs as a model of JOCD at the distal femur. First, stifle (knee) joints harvested from three juvenile miniature pigs underwent magnetic resonance imaging (MRI) to establish the vascular architecture of the distal femoral epiphyseal cartilage. Second, vessels supplying the axial or abaxial aspects of the medial femoral condyle were surgically interrupted in four additional juvenile miniature pigs, and the developing epiphyseal cartilage lesions were monitored using three consecutive MRI examinations over nine weeks. The miniature pigs were then euthanized, and their distal femora were harvested for histological evaluation. Vascular architecture of the distal femoral epiphyseal cartilage in the miniature pigs was found to be nearly identical to that of juvenile human subjects, characterized by separate vascular beds supplying the axial and abaxial aspects of the condyles. Surgical interruption of the vascular supply to the abaxial aspect of the medial femoral condyle resulted in ischemic cartilage necrosis (a precursor lesion of JOCD) in 75% (3/4) of the miniature pigs. Cartilage lesions were identified during the first MRI performed 3 weeks post‐operatively. No clinically apparent JOCD‐like lesions developed. In conclusion, miniature pigs are suitable for modeling JOCD precursor lesions. Further investigation of the model is warranted to assess induction of clinically apparent JOCD lesions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2130–2137, 2019     

非转流小型猪原位肝移植模型的建立及评价

目的建立标准化程度高、重复性和稳定性好的小型猪原位肝移植模型。方法选巴马小型猪为实验动物,在非体外静脉转流条件下行同种异体原位肝移植术,观察动物存活率及术中血流动力学、血气和生化指标的改变。结果在非体外静脉转流条件下行同种异体原位肝移植20例,平均手术时间为(181±25.8)min,平均无肝期(28.4±3.2)min。在无肝期,血流动力学和代谢发生急剧变化:平均动脉压(MAP)从无肝前期的(14.59±1.68)kPa(1cm H2O=0.098kPa)降至(5.87±0.91)kPa,中心静脉压(CVP)从(0.66±0.11)kPa降至(0.27±0.10)kPa;体温、pH、剩余碱(BE)及HCO3ˉ显著降低,心率及血清K+显著升高(P<0.05);随着门静脉和下腔静脉血流的开放,血流动力学及代谢紊乱即逐渐恢复正常。动物1周存活率为90%,16头动物存活2周以上。肝功结果:术后第1天ALT、AST和TBIL显著升高并达到峰值,第2天开始下降,第7天降至麻醉后水平。结论非转流条件下的小型猪同种异体原位肝移植模型具有标准化程度及手术成功率高、重复性和稳定性好的优点,是大型动物肝移植系列研究的理想动物模型。     

Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats

The aim of this study was to investigate the influence of N-acetylcysteine (NAC) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increase in mortality rate, pancreatic necrosis and serum activity of amylase, alanine aspartate transferase (ALT), interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and significant decrease of concentrations of calcium, blood pressure, urine output and pO(2). The use of NAC inhibited the changes in urine output, pO(2), tissue activity of MPO and MDA in pancreas and lungs, and the serum activity of IL-6, ALT, and serum concentrations of urea and calcium. NAC reduced the mortality and pancreatic damage. The use of NAC has a beneficial effect on the course of ANP in rats. It may be used in the treatment of acute pancreatitis.     

Effects of N-acetylcysteine on myoglobinuric-acute renal failure in rats

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 0 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group I before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.     

再灌注早期应用腺苷对离体缺血鼠心的保护作用

离体大鼠工作心脏模拟体外循环缺血停搏１２０分钟，观察复灌早期１μｍｏｌ／Ｌ腺苷的心肌保护作用。结果示实验组心功能恢复值明显高于对照组；心肌酶释放减少，冠脉流量增加；再灌４５分钟，心肌ＡＴＰ含量明显回升。提示复灌早期，腺苷通过改善心肌灌注，增加ＡＴＰ生成等对映血再灌注心肌发挥保护作用。     

含磷酸肌酸心脏停搏液对鼠供心的心肌保护作用

目的探讨含磷酸肌酸的心脏停搏液对离体心脏的保存效果，以延长供体心脏缺血的保存时间，提高心脏移植的效果。方法将20只Wistar大鼠随机分成两组，对照组（n=10）：使用冷晶体St．ThomasⅡ心脏停搏液灌注保护供心；实验组（n-10）：灌注含磷酸肌酸钠（2．5g／L）的冷晶体St．ThomasⅡ心脏停搏液保护供心。鼠心于低温保存4h后取心肌组织，测定心肌组织中三磷酸腺苷（ATP）含量和超氧化物歧化酶（SOD）活性。在光学显微镜和电子显微镜下观察心肌组织结构变化及线粒体水肿情况。结果供心冷藏保存4h后，实验组心肌组织中ATP含量明显高于对照组（2．75±0．99μmol／mg vs．1．77±0．86μmol／mg，P〈0．05）；SOD活性明显高于对照组（49．6±2．52U／mg vs．45．27±2．21U／mg，P〈0．05）。电子显微镜下观察：对照组心肌细胞核固缩，核膜内染色质凝聚、溶解，线粒体嵴间隙消失，间质血管内皮坏死；实验组心肌细胞核位于中心区，肌节各带结构清晰，肌质网扩张，闰盘各带连接结构清晰。结论含磷酸肌酸的心脏停搏液能明显增强供心的心肌保护作用。