Influence of ascorbic acid on BUN, creatinine, resistive index in canine renal ischemia-reperfusion injury

Renal ischemia as a course of renal transplantation is a common cause of renal dysfunction as renal failure. The purpose of this study was to investigate the influence of ascorbic acid on blood urea nitrogen (BUN), creatinine (Cr) and resistive index (RI) for dog models with renal ischemia-reperfusion (I/R) injury. Renal ischemia was induced on 6 Beagle dogs. The left kidney was exposed to normothermic ischemia for a short period at 30 min followed by reperfusion. On the blood Cr level and RI, there was no significant difference comparing both groups. 14 days after I/R injury a significant reduction on the blood BUN level was observed in the vehicle group (34.06 mg/dl) compared to that of ischemia induced treated group (10.3mg/dl) (p < 0.05). In conclusion, administration of ascorbic acid for renal ischemic-reperfusion injury had influence on blood BUN level, but it was not revealed the influence on blood Cr and RI.     

莲心碱对大鼠脑缺血再灌注损伤血清中IL-1、TNFa的影响

目的:观察莲心碱对大鼠局灶性脑缺血/再灌注损伤血清中白介素-1(IL-1)和肿瘤坏死因子a(TNFa)活性的影响,探讨其对大鼠脑缺血再灌注损伤保护作用的机制。方法:线栓法阻塞大鼠大脑中动脉2h/再灌注24h制备大鼠脑缺血再灌注损伤动物模型。将24只SD雄性大鼠,随机分为3组:假手术组、缺血再灌注组和莲心碱3mg·kg-1组,分别于术前30min、再灌注后、再灌注12h舌静脉注射莲心碱3mg·kg-1;再灌注24h后大鼠断头取血,分离血清,采用双抗体夹心ELISA法测定血清IL-1和TNFa的吸光度。结果:大鼠脑缺血2h,再灌注24h后,血清中IL-1和TNFa活性显著增加,莲心碱可显著降低缺血再灌注损伤大鼠血清IL-1和TNFa活性。结论:莲心碱可能通过降低IL-1和TNFa活性而发挥脑缺血的保护作用。     

橄榄苦苷对小鼠脑缺血再灌注损伤的保护作用

本研究为探讨橄榄苦苷联合依达拉奉对小鼠脑缺血再灌注损伤的影响及其保护作用机制,将50只健康小鼠分成假手术组、模型组、橄榄苦苷组、依达拉奉组、橄榄苦苷＋依达拉奉组。利用双侧颈总动脉结扎方法制备慢性脑缺血再灌注小鼠模型,造模后药物处理21 d,用放射免疫法检测脑组织肿瘤坏死因子α（TNF-α）、白细胞介素1（IL-1β）、白细胞介素10（IL-10）含量,用比色法检测脑组织ATP酶、髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性及丙二醛（MDA）含量,用免疫组织化学法及Western blotting法检测大脑皮层脑源性神经营养因子（BDNF）的表达。结果显示,与假手术组相比,模型组脑组织TNF-α、IL-1β、MDA的含量及MPO活性极显著升高（P<0.01）,IL-10、ATP酶、SOD、CAT水平均极显著降低（P<0.01）,大脑皮层BDNF表达水平极显著降低（P<0.01）。与模型组比较,橄榄苦苷或依达拉奉治疗后,脑组织TNF-α、IL-1β、MDA的含量及MPO活性极显著降低（P<0.01）,IL-10、ATP酶、SOD、CAT水平均极显著升高（P<0.01）,大脑皮层BDNF表达水平极显著升高（P<0.01）。橄榄苦苷和依达拉奉联合治疗后脑缺血再灌注损伤的恢复更加显著。综上所述,橄榄苦苷和依达拉奉对小鼠脑缺血再灌注损伤具有明显的保护作用,其机制可能与改善神经功能、减少自由基损伤和抑制炎症因子水平有关,橄榄苦苷和依达拉奉联合治疗可以发挥更好的作用。     

脂肪来源间充质干细胞条件培养基对小型猪腹腔镜肝损伤氧化应激反应的影响

旨在探究脂肪来源间充质干细胞条件培养基（adipose-derived mesenchymal stem cells-conditioned medium，ADSCs-CM）对小型猪肝损伤氧化应激反应的影响，作者选取24头健康小型猪，随机分为4组，每组6只，分别为模型组（IRI）、DMEM对照组（DMEM）、ADSCs-CM治疗组（CM）和ADSCs治疗组（ADSCs）。4组均通过腹腔镜技术建立小型猪肝缺血再灌注（ischemia reperfusion，IR）合并部分肝切除的肝损伤模型，IRI组移植生理盐水，DMEM组移植浓缩的基础培养基，CM组移植浓缩的脂肪来源间充质干细胞培养基，ADSCs组移植脂肪间充质干细胞。各组分别于术前、术后1、3、7 d采集血液与肝组织样本，使用肝功能检测试剂盒对血清中总胆红素（T-BIL）、乳酸脱氢酶（LDH）、总蛋白（TP）进行检测；使用氧化应激检测试剂盒对肝组织中丙二醛（MDA）、髓内过氧化物酶（MPO）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）进行检测。结果显示：术后1、3 d：模型组和对照组肝功能严重损伤，发生明显氧化应激反应，CM和ADSCs治疗组显著促进肝功能的恢复，且氧化应激相应指标较模型组和对照组表达明显下降。术后7 d，各组基本恢复到术前水平。结果显示：腹腔镜肝缺血再灌注合并肝部分切除损伤可致小型猪发生氧化应激反应，脂肪来源间充质干细胞及其条件培养基均可改善肝损伤后的氧化应激反应。     

Astragalus injection inhibits expression of Apaf-1 in rat hippocampus after cerebral ischemia and reperfusion

AIM: To investigate the effect of Astragalus injection on the expression of apoptotic protease-activating factor 1 (Apaf-1) in the hippocampus of global cerebral ische-mia-reperfusion rats. METHODS: Male SD rats were randomly divided into 4 groups with 30 each: sham operation group, cerebral ischemia-reperfusion group, cerebral ischemia-reperfusion+Astragalus injection group, and cerebral ischemia-reperfusion+vehicle group. The global cerebral ischemia-reperfusion model of the rats was established by 4-vessel occlusion. The rats in cerebral ischemia-reperfusion group, cerebral ischemia-reperfusion+Astragalus injection group and cerebral ischemia-reperfusion+vehicle group were further divided into 7 subsets, according to the reperfusion time of 0 h, 0.5 h, 2 h, 6 h, 24 h, 72 h and 120 h. After reperfusion, the brains were removed at the corresponding time points. The protein expression of Apaf-1 in hippocampal neurons was detected by immunohistochemistry and Western blotting. The mRNA expression of Apaf-1 was observed by RT-PCR. RESULTS: Compared with sham operation group, the expression of Apaf-1 at mRNA and protein levels at all time points except 0 h and 120 h increased obviously in cerebral ischemia-reperfusion group (P<0.05). Compared with cerebral ischemia-reperfusion group, the expression of Apaf-1 at mRNA and protein levels at all time points except 0 h and 120 h decreased obviously in cerebral ischemia-reperfusion+Astragalus injection group (P<0.05). However, those in cerebral ischemia-reperfusion+vehicle group had no obvious change (P>0.05). CONCLUSION: Astragalus injection inhibits the expression of Apaf-1 at mRNA and protein levels in hippocampus of global cerebral ischemia-reperfusion rats, thus inhibiting the apoptosis of hippocampal neurons.     

Lactulose preconditioning protects against intestinal ischemia-reperfusion injury in rats

AIM: To investigate the protective effect of lactulose preconditioning on intestinal ischemia-reperfusion (IR) injury in rats. METHODS: Thirty Sprague-Dawley rats were randomly divided into 3 groups: sham operation group, IR group and IR plus lactulose preconditioning group. Lactulose was intragastrically administered in lactulose group 7 days prior to operation, and the equal volume of saline was administered in the other 2 groups. The intestinal IR injury was induced in IR group and IR+lactulose group using bulldog clamps on superior mesenteric artery by 30 min of ischemia followed by 60 min of reperfusion. Following reperfusion, the serum samples were collected for estimating the levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and IL-1β. Segments of terminal jejunum were rapidly fixed in 4% paraformaldehyde, and HE staining was applied to assess the histopathology. Apoptosis in intestinal epithelium was determined by the technique of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The samples of terminal jejunum were also taken for measuring malondialdehyde,superoxide dismutase and the expression of cleaved caspase-3. RESULTS: Lactulose preconditioning significantly attenuated the severity of intestinal IR injury, with inhibition of IR-induced apoptosis. Moreover, lactulose preconditioning significantly limited the release of cytokines and lipid oxidation. CONCLUSION: Lactulose preconditioning has a protective effect on intestinal ischemia reperfusion by inhibiting IR-induced apoptosis and oxidative stress.     

Protective effect of atorvastatin on blood brain barrier in rats with focal cerebral ischemia-reperfusion injury

AIM: To explore the protective effects of atorvastatin on blood brain barrier(BBB) in cerebral ischemia-reperfusion(IR) injury and the potential mechanisms involved. METHODS: SD rats were divided into sham group, IR group and atorvastain group. Intraluminal suture method was used to establish cerebral IR model, and the ischemic brain was reperfused for 72 h after the occlusion. The rats in atorvastatin group were administered with atorvastatin(20 mg·kg^-1·d^-1) by gavage once a day for 3 consecutive days after operation. At 72 h after reperfusion, neurological function scores, the water content of the brain tissue, Evans blue(EB) content of ischemic hemisphere, the expression of tight junction(TJ)-associated protein occludin and inflammation factor phosphatidylinositiol 3-kinase-p110 gamma(PI3K-p110γ) were tested and analyzed. RESULTS: In IR group, the rats showed elevated neurological function scores(P<0.01), brain tissue water content(P<0.01) and EB content(P<0.01), accompanied with the down-regulation of occludin expression(P<0.01) and up-regulation of PI3K-p110γ(P<0.01) at 72 h after reperfusion. Compared with IR group, decreased brain edema(P<0.01) and EB leakage(P<0.01) were observed in atorvastatin group, accompanied with increased occludin expression(P<0.01) and decreased PI3K-p110γ expression(P<0.01). However, no statistical difference of the neurological function scores between the 2 groups was observed. CONCLUSION: Atorvastain attenuates cerebral IR injury, which may be associated with the inhibition of inflammatory reactions and the up-regulation of TJ-asso-ciated proteins to maintain the stability of BBB.     

Traditional Chinese medicine YHTJF prevents lung ischemia-reperfusion injury via caspase-12 pathway

AIM: To explore whether Yiqi Huoxue Tongluo Jiedu Fang (YHTJF) decreases the injury during lung ischemia-reperfusion (I/R) in the mice though caspase-12 pathway.METHODS: C57BL/6J male mice (n=70) were randomly divided into 7 groups: control, carboxyl methyl cellulose-Na (CMC-Na), sham, I/R, YHTJF-low (L), YHTJF-middle (M) and YHTJF-high (H) groups. YHTJF was injected intraperitoneally at 46, 92 and 184 mg/kg every day in YHTJF-L, YHTJF-M and YHTJF-H groups, respectively. The carboxyl methyl cellulose-Na was administered with the same volume of YHTJF-L in control, sham and I/R groups. After 3 h-reperfusion, the left lung tissue was harvested to determine the lung wet/dry weight ratio (W/D), the total lung water content (TLW), and index of quantitative evaluation (IQA) of alveolar damage. Morphological observation and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) were applied to evaluate the structural changes and the apoptosis index (AI) of the lung tissues, respectivety. The expression of caspase-12 and glucose-regulated protein 78 (GRP78) at protein and mRNA levels in the lung tissues were detected by Western blot and RT-PCR. RESULTS: Compared with control, the W/D, TLW, IQA, AI, and the expression of caspase-12 and GRP78 at mRNA and protein levels in I/R group obviously increased (P<0.01), while no significant difference was observed between control and sham groups. Compared with I/R group, the above indexes (except GRP78) in YHTJF-L, YHTJF-M and YHTJF-H groups were all decreased (P<0.01). CONCLUSION: YHTJF may attenuate the I/R injury of the lung by inhibition of apoptosis via caspase-12 pathway.     

Ω3 Supplementation and Intermittent Hypobaric Hypoxia Induce Cardioprotection Enhancing Antioxidant Mechanisms in Adult Rats

Intermittent hypobaric hypoxia (IH) is linked with oxidative stress, impairing cardiac function. However, early IH also activate cardio-protective mechanisms. Omega 3 fatty acids (Ω3) induce cardioprotection by reducing infarct size and reinforcing antioxidant defenses. The aim of this work was to determine the combined effects of IH and Ω3 on cardiac function; oxidative balance and inflammatory state. Twenty-eight rats were randomly divided into four groups: normobaric normoxia (N); N + Ω3 (0.3 g·kg⁻¹·day⁻¹); IH; and IH + Ω3. IH was induced by 4 intercalate periods of hypoxia (4 days)—normoxia (4 days) in a hypobaric chamber during 32 days. At the end of the exposure, hearts were mounted in a Langendorff system and subjected to 30 min of ischemia followed by 120 min of reperfusion. In addition, we determined HIF-1α and ATP levels, as well as oxidative stress by malondialdehyde and nitrotyrosine quantification. Further, the expression of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase was determined. NF-kappaB and myeloperoxidase levels were assessed in the hearts. Relative to N hearts, IH improved left ventricular function (Left ventricular developed pressure: N; 21.8 ± 3.4 vs. IH; 42.8 ± 7.1 mmHg; p < 0.05); reduced oxidative stress (Malondialdehyde: N; 14.4 ± 1.8 vs. IH; 7.3 ± 2.1 μmol/mg prot.; p < 0.05); and increased antioxidant enzymes expression. Supplementation with Ω3 induces similar responses as IH group. Our findings suggest that both, IH and Ω3 in an independent manner, induce functional improvement by antioxidant and anti-inflammatory mechanisms, establishing cardio-protection.