Effects of sulfur dioxide on alveolar macrophage apoptosis in acute lung injury induced by limb ischemia/reperfusion in rats / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of sulfur dioxide (SO2) on the apoptosis of alveolar macrophage (AM) in lung protection of limb ischemia/reperfusion (I/R) induced acute lung injury (ALI), and to find a new target for the control of inflammatory response.@*METHODS@#Twenty pathogen-free, adult male Sprague-Dawley (SD) rats (180-230 g) were used in this study. Five rats were to be used for limb ischemia/reperfusion, then plasma was extracted as ischemia/reperfusion serum stimulation. Fifteen rats were to be used for extracting AM by bronchoalveolar lavage. The AM was isolated and cultured, then the cell count was adjusted to 1×106/mL, and randomly divided into the following 4 groups (n=6): control group, I/R group, SO2 group, and I/R+SO2 group. The I/R group was given ischemia/reperfusion serum (500 μg/L) to stimulate 6 h; the SO2 group was given an SO2 donor, Na2SO3/NaHSO3 [(0.54 mmol/kg) / (0.18 mmol/kg)]; and the I/R+SO2 group was given the same ischemia/reperfusion serum and Na2SO3/NaHSO3 at the same time. The level of mitochondrial membrane potential, the state of mitochondrial permeability transition pore (mPTP), the rate of AM apoptosis, the expression of Bcl-2 and Caspase-3 proteins were detected by flow cytometry, microplate reader and Western blotting.@*RESULTS@#Compared with the control group, in the I/R group, the ratio of red to green fluorescence and the absorbance decreased significantly, the percentage of apoptotic cells increased obviously, the apoptotic rate was 43.81%±2.40%, Caspase-3 protein expression increased, Bcl-2 protein expression decreased. While compared with the I/R group, in the I/R+SO2 group, the ratio of red to green fluorescence and the absorbance increased significantly; the apoptotic rate decreased to 37.01%±1.93%, Caspase-3 protein expression decreased, Bcl-2 protein expression increased.@*CONCLUSION@#Exogenous SO2 has the effect of accelerating AM apoptosis by stimulating mPTP to open and mitochondrial membrane potential to decrease; besides, exogenous SO2 could stimulate AM to secrete more anti-inflammatory cytokines and less inflammatory cytokines. In conclusion, exogenous SO2 can reduce macrophage apoptosis by inhibiting mitochondrial pathways.

Locking plate versus external fixation for type C distal radius fractures: A meta-analysis of randomized controlled trials / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>Distal radial fracture is one of the most common fractures. Up to now, locking plates (LP) and external fixation (EF) are two conventional surgical approaches to type C radius fracture. Which method is superior has not yet reached a consensus. We try to assess the clinical effectiveness of the two interventions by this meta-analysis.</p><p><b>METHODS</b>We used network to search the PubMed, Embase, and Cochrane Medical Library of randomized controlled clinical trials about the type C distal radius fractures performed according to the search strategy mentioned in Cochrane Handbook 5.1.0 from Jan. 2005 to Jan. 2016. Patients in the experimental group were used LP, in the control group were included EF and other surgical approaches. Publication language was restricted to English. Studies that patient population and surgical indication did not define had been excluded. Studies must report at least one of the outcomes as follow: radial inclination, palmar tilt, ulnar variance, range of wrist flexion and extension, and range of wrist supination and pronation. The trials in which participants included children were excluded. We used Jadad study scores to appraise the study.</p><p><b>RESULTS</b>Seven studies included 162 patients (LP group) and 190 patients (EF group). We compared the radial inclination, palmar tilt, ulnar variance, range of wrist flexion and extension, and range of wrist supination and pronation. The radial inclination were revealed a difference favoring LP over EF [WMD = 1.84, 95% CI (0.17, 3.50), p = 0.03] and the palmar tilt and ulnar variance was no significant difference between the two groups [(WMD = 3.61, 95% CI (0.00, 7.23), p = 0.05; WMD = 0.05, 95% CI (-0.99, 1.09), p = 0.93]. The functional activities of range of flexion and extension and range of supination and pronation between the two groups was no difference [WMD = 10.04, 95% CI (-6.88, 26.96), p = 0.24; WMD = 12.53, 95% CI (-9.99, 35.06), p = 0.28].</p><p><b>CONCLUSION</b>Locking plate and external fixation is feasible to heal radius type C fracture. We found the small difference between the two groups on imaging examination. The locking plate has the advantage on maintaining reduction, however no significant difference regarding outcomes has been found between the two groups.</p>

Functional Outcome of Pronation-External Rotation-Weber C Ankle Fractures with Supracollicular Medial Malleolar Fracture Treated with or without Syndesmotic Screws: A Retrospective Comparative Cohort Study / 中华医学杂志(英文版)

<p><b>Background</b>In treatment of ankle fracture, intraoperative stress tests are used to assess the syndesmotic injury and instability. However, the optimized timing of the strees test should be applied whether in pre- or post-bony fixation during operation is seldom be reported in previous studies. The different strategies on stress test timing would exhibit opposite results within a type of pronation-external rotation (PER) fractures with supracollicular medial malleolar (SMM) fractures. This study was designed to assess the 3-year functional outcomes of the special PER fractures with or without a syndesmotic transfixation based on the results of two different intraoperative stress test strategies.</p><p><b>Methods</b>This retrospective cohort study included 61 PER injury-Weber C ankle fractures combined with SMM fractures who were treated in Beijing Jishuitan Hospital between 2013 and 2014 and followed up for 3 years. Stress test was performed twice intraoperatively. A positive intraoperative stress test before bony fixation and a negative intraoperative stress test after bony fixation were found in these included patients. Twenty-nine patients (Group 1) were treated without a supplemental syndesmotic screw fixation, according to the negative intraoperative stress test after bony fixation, while 32 patients (Group 2) were treated with an additional syndesmotic screw fixation based on the positive intraoperative stress test before bony fixation. The American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and Visual Analog Scale (VAS) for pain scores were the main measurements of outcome. The statistical index of demographic data, fracture morphologic data, time interval of follow-up, AOFAS and VAS were recorded and assessed by SPSS 21.0 software through Fisher exact tests and one-way analysis of variance. The associations between the main outcomes and influential factors were evaluated by linear regression models.</p><p><b>Results</b>We observed no difference in the distribution of age, sex, presence of associated posterior malleolus (PM), fracture dislocation, and fixation of associated PM between two treatment groups. With the numbers available, no statistically significant association could be detected with regard to the AOFAS (Group 1 vs. Group 2, 96.72 ± 6.20 vs. 94.63 ± 8.26, F = 1.24, P = 0.27) and VAS (Group 1 vs. Group 2, 1.47 ± 2.14 vs. 0.72 ± 1.49, F = 2.44, P = 0.12) in association with two strategies.</p><p><b>Conclusions</b>The present study indicates no difference to the use of the syndesmotic screw in terms of the functional outcome between syndesmosis transfixation and no-fixation patients among PER-Weber C ankle fracture patients with SMM fracture after 3-year follow-up. More attention should be paid to pre- and post-bony-fixation intraoperative stress tests and the morphology of medial malleoli fractures in ankle fractures.</p>

Low dose of lipopolysaccharide pretreatment can alleviate the in?ammatory response in wound infection mouse model / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>To assess the effects of lipopolysaccharide (LPS) pretreatment on wound infection mouse model and evaluate the biological safety of the optimal pretreatment dose in vivo.</p><p><b>METHODS</b>Mice were pretreated with LPS of different doses at 48 and 24 h before femoral medial lon- gitudinal incision was made and infected with different bacteria.</p><p><b>RESULTS</b>It is showed that 0.5 mg/kg/time of LPS pretreatment can significantly alleviate the inflammation in mouse model infected with methicillin-resistances Staphylococcus aureus, methicillin-sensitive S. aureus, Pseudomonas aeruginosa,or Escherichia coli compared with doses of 0.25 mg/kg/time, 1 mg/ kg/time, and 1.5 mg/kg/time.</p><p><b>CONCLUSIONS</b>LPS pretreatment can alleviate the inflammation in mouse model and the optimal dose is 0.5 mg/kg/time, and meanwhile it does not damage organs' function.</p>

Biomechanical Study of the Fixation Strength of Anteromedial Plating for Humeral Shaft Fractures / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Open reduction and internal fixation with plate and screws are the gold standard for the surgical treatment of humeral shaft fractures, this study was to compare the mechanical properties of anteromedial, anterolateral, and posterior plating for humeral shaft fractures.</p><p><b>METHODS</b>A distal third humeral shaft fracture model was constructed using fourth-generation sawbones (#3404, composite bone). A total of 24 sawbones with a distal third humeral shaft fracture was randomly divided into three Groups: A, B, and C (n = 8 in each group) for anteromedial, anterolateral, and posterior plating, respectively. All sawbones were subjected to horizontal torsional fatigue tests, horizontal torsional and axial compressive fatigue tests, four-point bending fatigue tests in anteroposterior (AP) and mediolateral (ML) directions and horizontal torsional destructive tests.</p><p><b>RESULTS</b>In the horizontal torsional fatigue tests, the mean torsional angle amplitude in Groups A, B, and C were 6.12°, 6.53°, and 6.81°. In horizontal torsional and axial compressive fatigue tests, the mean torsional angle amplitude in Groups A, B, and C were 5.66°, 5.67°, and 6.36°. The mean plate displacement amplitude was 0.05 mm, 0.08 mm, and 0.10 mm. Group A was smaller than Group C (P < 0.05). In AP four-point bending fatigue tests, the mean plate displacement amplitude was 0.16 mm, 0.13 mm, and 0.20 mm. Group B was smaller than Group C (P < 0.05). In ML four-point bending fatigue tests, the mean plate displacement amplitude were 0.16 mm, 0.19 mm, and 0.17 mm. In horizontal torsional destructive tests, the mean torsional rigidity in Groups A, B, and C was 0.82, 0.75, and 0.76 N·m/deg. The yielding torsional angle was 24.50°, 25.70°, and 23.86°. The mean yielding torque was 18.46, 18.05, and 16.83 N·m, respectively.</p><p><b>CONCLUSIONS</b>Anteromedial plating was superior to anterolateral or posterior plating in all mechanical tests except in AP four-point bending fatigue tests compared to the anterolateral plating group. We can suggest that anteromedial plating is a clinically safe and effective way for humeral shaft fractures.</p>

Macroscopic and histological evaluations of meniscal allograft transplantation using gamma irradiated meniscus: a comparative in vivo animal study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many studies suggest that the gamma irradiation decreases allograft strength in a dose-dependent manner. However, no study has demonstrated that this decrease in strength translates into higher failure rate in meniscal allograft transplantation (MAT). The aim of this study was to investigate the effects of gamma irradiation on macroscopic and histological alterations of transplanted meniscal tissue and joint cartilage after MAT.</p><p><b>METHODS</b>Medial total meniscectomies were performed on the right knees of 60 New Zealand white rabbits. All meniscal allografts were divided into three groups (20 in each group) and then sterilized with 0 Mrad, 1.5 Mrad, or 2.5 Mrad of gamma irradiation. For each group, 5 menisci were randomly chosen for scanning electron microscopic (SEM) analysis and the remaining 15 were prepared for MAT surgeries. Forty-five right knees received MAT surgeries (0 Mrad group, 1.5 Mrad group, 2.5 Mrad group, 15 in each group), whereas the remaining 15 only received medial meniscectomy (Meni group). The left knees of the Meni group were chosen as the Sham group (n = 15). All the rabbits were sacrificed at week 24 postoperatively. Cartilage of the medial compartment of each group was evaluated macroscopically using the International Cartilage Repair Society (ICRS) score and then histologically using the Mankin score based on the Masson Trichrome staining.</p><p><b>RESULTS</b>The SEM analysis confirmed that the meniscal collagen fibers would be significantly damaged as the dose of gamma irradiation increased. At week 24, the overall scores of macroscopic evaluations of the transplanted meniscal tissue showed no significant differences among the three groups receiving MAT surgeries, except for 2 in the 2.5 Mrad group presented partial radial tears at midbody. The ICRS scores and the Mankin scores showed the lowest in the Sham group and the highest in the Meni group (P < 0.05). For the three groups receiving MAT surgeries, the 2.5 Mrad group showed significant higher ICRS scores and Mankin scores than both the 0 Mrad group and the 1.5 Mrad group (P < 0.05). Whereas the 1.5 Mrad group presented similar results to the 0 Mrad group concerning both the ICRS scores and the Mankin scores.</p><p><b>CONCLUSIONS</b>The current in vivo animal study proved that although the meniscal collagen fibers were damaged after gamma irradiation, the failure rate of MAT surgeries might not significantly increase if the irradiation dose was <1.5 Mrad for New Zealand white rabbits.</p>

Case-control study on cable-pin system in the treatment of olecranon fractures / 中国骨伤

<p><b>OBJECTIVE</b>To prospectively evaluate the clinical result of Cable-Pin system in the treatment of olecranon fractures and compare with tension band wiring (TBW) method.</p><p><b>METHODS</b>From March 2008 to June 2010,65 patients with olecranon fractures were divided into two groups: 32 patients in Cable-Pin group were treated with Cable-Pin system, including 18 males and 14 females, ranging in age from 21 to 69 years, with an average of (53.69 +/- 13.42) years; 33 patients in TBW group were treated with Kirschner tension bend, including 20 males and 13 females, ranging in age from 20 to 70 years, with an average of (53.18 +/- 13.36) years. The incision length, operation time, the amounts of hemoglobin after operation, fracture healing time, complications and HSS elbow scores were recorded and analyzed statistically. The follow-up period ranged from 12 to 24 months, with an average period of 18.4 months.</p><p><b>RESULTS</b>There were statistical differences (P<0.05) in fracture healing time (t= 2.588, P=0.012), complication rate (chi2=4.534, P=0.033) and HSS elbow joint scores (Z=-2.039, P=0.041) between two groups, which all were superior to TBW in Cable-Pin group. There was no statistical differences (P>0.05) in the length of incision (t= 0.416, P=0.679), operation time (t=0.816, P=0.417) and the postoperative amounts of hemoglobin (t=-0.553, P=0.294) between two groups.</p><p><b>CONCLUSION</b>Cable-Pin system is an easy and reliable method for the treatment of olecranon fractures with less complications and better functions than TBW.</p>

Osteoprotegerin and osteoprotegerin ligand expression during human marrow stromal cell differentiation and their effect on osteoclast formation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) play an important role in human bone metabolism. The aim of this research was to detect the expression of OPG and OPGL during human marrow stromal cells (hMSC) differentiation into osteoblasts (OB), and to observe their effect on osteoclasts (OC) formation in vitro to investigate bone metabolism mechanisms.</p><p><b>METHODS</b>hMSCs were obtained from human bone marrow specimens using gradient centrifugation method, before being purified and incubated with differentiation medium to develop along the human osteoblasts (hOB) pathway. Morphology observation, biochemical detection and cell staining were performed during hMSC differentiation. OPG and OPGL mRNA levels were detected by reverse transcription-polymerase chain reaction. OPG and OPGL protein expression were determined by Western blotting. We further obtained OC progenitor cells from mice bone marrow and co-cultured with differentiating MSCs. We assessed the effect of OPG and OPGL on OC formation by identifying tartrate resistant acid phosphatase (TRAP) positive multinuclear cells.</p><p><b>RESULTS</b>Optimal hMSC survival and purification were observed, along with stable biochemical indexes. Alkaline phosphatase secretion increased significantly and mineralization nodules appeared in the process of cell differentiation. OPG mRNA and protein level increased significantly, while OPGL mRNA and protein level decreased. Average levels of OPG mRNA and protein were about 2.5-fold higher than the control, while OPGL mRNA and protein levels were reduced by about one-half. In the group co-culturing with undifferentiated MSC or added OPGL, we found TRAP positive and multi- nuclear OC formation. However, OC formation was absent in the group co-culturing with differentiated MSC or added OPG.</p><p><b>CONCLUSIONS</b>During hMSC differentiation into hOB, OPG secretion increased rapidly and OPGL production decreased significantly. The OPG/OPGL ratio was also increased, while OC formation was inhibited and bone absorption decreased. Thus, regulation of the OPG/OPGL ratio may be important in controlling MSC differentiation, OB and OC formation in succession involved in bone metabolism.</p>

Protection of carbon monoxide-releasing molecule against lung injury induced by limb ischemia-reperfusion / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To observe the role and mechanism of CO-releasing molecule (CORM)-2 in lung injury induced by ischemia-reperfusion (IR) of hind limbs in rats.</p><p><b>METHODS</b>A rat model of lung injury induced by IR of hind limbs was established. A total of 40 Sprague Dawley (SD) rats were randomly divided into 5 groups (n equal to 8): sham, sham + CORM-2, IR, IR + CORM-2 and IR + dimethyl sulfoxide (DMSO). Rats in the IR group received hind limb ischemia for 2 hours and reperfusion for 2 hours, rats in the sham group underwent sham surgery without infrarenal aorta occlusion, rats in the IR+CORM-2 group and in the sham + CORM-2 group were given CORM-2 (10 micromol/kg intravenous bolus) 5 minutes before reperfusion or at the corresponding time points, while rats in the IR + DMSO group was treated with the same dose of vehicle (DMSO) at the same time. The lung tissue structure, polymorphonuclear neutrophil (PMN) count, wet-to-dry weight ratio (W/D), malondialdehyde (MDA) content, myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) expression,IkBa degradation and nuclear factor (NF)-kB activity in the lungs were assessed.</p><p><b>RESULTS</b>As compared with the sham group, lung PMNs number, W/D, MDA content, MPO activity, ICAM-1 expression and NF-kB activity significantly increased in the IR group, but the level of IkBa decresed (P less than 0.01). Compared with the IR group, lung PMNs number, W/D, MDA content, MPO activity and ICAM-1 expression significantly decreased in the IR+COMR-2 group (P less than 0.01), while the level of IkBa increased.</p><p><b>CONCLUSIONS</b>These data demonstrate that CORM-2 attenuates limb IR-induced lung injury through inhibiting ICAM-1 protein expression, NF-kB pathway and the leukocytes sequestration in the lungs following limb IR in rats, suggesting that CORM-2 may be used as a therapeutic agent against lung injury induced by limb IR.</p>

Role of polymorphonuclear neutrophil in exogenous hydrogen sulfide attenuating endotoxin-induced acute lung injury / 生理学报

The animal model of acute lung injury (ALI) caused by intravenous injection of lipopolysaccharides (LPS) and cultured human peripheral blood polymorphonuclear neutrophil (PMN) were used to study the effects of sodium hydrosulfide (NaHS), hydrogen sulfide (H2S) donor, on LPS-induced PMN accumulation, microvascular permeability and PMN apoptosis. Control group, NaHS group, LPS group and LPS + NaHS group were established both in in vivo and in vitro studies. Microvascular permeability, PMN accumulation in lung and apoptosis of PMN were detected. The results showed that: (1) In in vivo study, PMN accumulation in lung, the protein content in bronchoalveolar lavage fluid (BALF) and the Evans blue dye in lung tissue of LPS group were markedly higher than those of both sham operation group and LPS + NaHS group (P<0.05, P<0.01); (2) In in vitro study, the apoptotic rates of PMN in LPS group and NaHS group were significantly higher than that in control group (P<0.01), while compared with LPS group, LPS + NaHS group showed significantly higher apoptotic rate (P<0.01). These results suggest that NaHS attenuates LPS-induced microvascular permeability and alleviates ALI. PMN apoptosis induced by NaHS is possibly one of the potential mechanisms underlying the decrease of PMN accumulation in lung tissue.

Ameliorative effects of exogenous sulfur dioxide on lipopolysaccharide-induced acute lung injury in rats / 生理学报

To investigate the influence of sulfur dioxide (SO₂) on lipopolysaccharide (LPS)-induced acute lung injury (ALI), we examined the influence of exogenous SO₂ on pulmonary tissue inflammatory response. A rat model of ALI induced by intravenous (IV) injection of LPS was developed. Male Sprague-Dawley (SD) rats were divided into four groups randomly: control group, LPS group, LPS plus SO₂ group (IV injection of 0.5 mL Na₂SO₃/NaHSO₃ 10 min before LPS administration) and SO₂ group (only given Na₂SO₃/NaHSO₃). Animals were sacrificed 6 h after agent administration. Lung weight/body weight ratio (LW/BW) was measured and calculated. Morphological changes of lung tissues were observed. The number of polymorphonuclear neutrophil (PMN) in the bronchoalveolar lavage fluid (BALF), intercellular adhesion factor-1 (ICAM-1) expression in the lung tissue and IL-1, IL-6 and IL-10 levels in the serum were tested. The results showed that, compared to control rats, the LPS-treated rats had severe injuries of lung tissues and an increased LW/BW, increased index of quantitative assessment (IQA) score, increased PMN number in the BALF, increased ICAM-1 expression in the lung tissue and increased IL-1, IL-6 and IL-10 levels in the serum 6 h after LPS injection. Administration of the SO₂ donor, Na₂SO/₃NaHSO₃, into LPS-treated rats reduced the LW/BW, PMN number and ICAM-1 expression, and alleviated the degree of ALI (measured by the IQA score). In addition, Na₂SO₃/NaHSO₃ decreased IL-1 and IL-6 levels, but increased IL-10 level in the serum. There were no significant differences in the above indexes between SO₂-treated rats and control rats. These results suggest that exogenous SO₂ could inhibit the pulmonary tissue inflammatory response in rats with LPS-induced ALI.

Changes of iNOS genes expression in liver following ischemia and reperfusion of limbs and their significance in rats / 中国应用生理学杂志

<p><b>AIM</b>To detect the changes of inducible nitric oxide synthase (iNOS) expression in liver following ischemia/reperfusion (I/R) of hindlimbs and to elucidate their significance.</p><p><b>METHODS</b>I/R was established using the occlusion of the femoral arteries for 4 h and reopening for 2-24 h in rats. The expression of iNOS mRNA, and iNOS protein and the nitrotyrosine (NT), a marker of peroxynitrite (ONOO-), in liver tissue were detected with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively. The liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents were spectrophotometrically measured. The observation of pathologic changes of liver was made following the inhibition of iNOS by aminoguanidine (AG).</p><p><b>RESULTS</b>Compared with control groups, the relative expression level of iNOS mRNA significantly increased in I/R group. There were more iNOS positive hepatocytes and more NT positive hepatocytes in I/R group than control groups. The contents of MDA markedly increased, while the activity of SOD significantly decreased in I/R group, compared with those in the control groups. The pathologic changes of rat liver became milder in I/R group following the inhibition of iNOS by AG.</p><p><b>CONCLUSION</b>The expressions of iNOS mRNA and protein in liver are significantly upregulated, excess induction of iNOS-NO is contributed to the liver injury during the I/R of hindlimbs.</p>

Changes of HO-1 genes expression in liver following ischemia/reperfusion of limbs and their significance in rats / 中国应用生理学杂志

<p><b>AIM</b>To detect the changes of inducible heme oxygenase (HO-1) expression in liver following ischemia/reperfusion (I/R) of hindlimbs and to elucidate their significance.</p><p><b>METHODS</b>I/R was established using the occlusion of the femoral arteries for 4h and reopening for 2-24 h in rats. The expression of HO-1 mRNA and HO-1 protein in liver tissue were detected with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical technique, respectively. The observation of pathologic changes of liver was made following the inhibition of HO-1 by zinc protoporphyrin (ZnPP).</p><p><b>RESULTS</b>Compared with control groups, the relative expression level of HO-1 mRNA significantly increased in I/R group. There were more HO-1 positive hepatocytes in I/R group than control groups. The pathologic changes of liver tissue became more severe in I/R + ZnPP group.</p><p><b>CONCLUSION</b>The expressions of HO-1 mRNA and protein in liver tissue are significantly upregulated, induction of HO-1 is involved in protection for hepatocytes during the I/R of hindlimbs.</p>

Change and role of heme oxygenase-1 in injured lungs following limb ischemia/reperfusion in rats / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the change and role of heme oxygenase-1 (HO-1) in injured lungs following limb ischemia/reperfusion in rats.</p><p><b>METHODS</b>A total of 96 healthy male Sprague-Dawley rats, weighing 250-300 g, were used in this study. Hind limb ischemia was made on 40 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, then limb reperfusion for 0, 4, 8, 16 and 24 hours (n=8 in each time point) was performed, respectively. Other 8 rats undergoing full surgical operation including isolation of the infrarenal aorta without occlusion were taken as the sham operation group. Lung tissues were obtained from the 48 animals and Northern blotting and Western blotting were employed to measure the changes of HO-1 mRNA and protein expression, respectively. Immunohistochemistry technique was used to determine the cell types responsible for HO-1 expression after limb ischemia/reperfusion. Then hind limb ischemia was made on other 12 rats through clamping the infrarenal aorta for 2 hours with a microvascular clip, among whom, 6 rats were given zinc protoporphyrin (ZnPP), an inhibitor of HO. Then limb reperfusion for 16 hours was performed on all the 12 rats. And other 12 rats underwent full surgical operation including isolation of the infrarenal aorta without occlusion, among whom, 6 rats were then given ZnPP. Then lung tissues were obtained from the 24 animals and lung injury markers, lung histology, polymorphonuclear leukocyte (PMN) count and malondialdehyde (MDA) content were detected, respectively. HO activity was determined through measuring the carboxyhemoglobin (COHb) level in artery blood with a CO-oximeter after limb ischemia/reperfusion. And the animal mortality was observed on the other 24 rats.</p><p><b>RESULTS</b>Northern blotting analysis showed that HO-1 mRNA increased significantly at 4 hours after reperfusion, peaked at 16 hours, and began to decrease at 24 hours. In contrast, no positive signal was observed in the sham and simple ischemia animals. Increased HO-1 mRNA levels were accompanied by similar increases in HO-1 protein. Lung PMNs and MDA content increased significantly at 4, 8, 16 and 24 hours after reperfusion, compared with the sham controls (P<0.001), while they decreased in rats with reperfusion for 16 hours when compared with rats with reperfusion for 4 hours (P<0.001). Immunohistochemical studies showed that HO-1 was expressed in a variety of cell types, including the airway epithelia, alveolar macrophages and vascular smooth muscular cells. The blood COHb level and animal mortality increased significantly after limb ischemia/reperfusion compared with the sham controls (P<0.001). ZnPP administrated to the ischemia/reperfusion animals led to a decrease in the COHb level and an increase in lung PMN number, MDA content and animal mortality (P<0.001 compared with ischemia/reperfusion group), and the lung injury was aggravated.</p><p><b>CONCLUSIONS</b>Limb ischemia/reperfusion up-regulates pulmonary HO-1 expression, which serves as a compensatory protective response to the ischemia/reperfusion-induced lung injury in rats.</p>

Endogenous carbon monoxide attenuates lung injury following ischemia-reperfusion in the hind limbs of rats / 生理学报

To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in the lung injury as assessed by lung histology, polymorphonuclear count, malondialdehyde content and wet-to-dry weight ratio following ischemia-reperfusion (I/R) of hind limbs, zinc protoporphyrin (ZnPP), an inhibitor of HO activity, was used, and the lung HO activity and blood carboxyhemoglobin (COHb) level were measured. The results showed that HO activity and COHb level were increased significantly and lung injury occurred after limb I/R. After administration of ZnPP, the lung injury was further aggravated while the HO activity and COHb level were significantly decreased. These findings suggest that upregulation of HO activity followed by subsequent CO production attenuates the lung injury induced by limb I/R in rats.