ObjectiveTo investigate the effects of phenethyl isothiocyanate (PEITC) on apoptosis and proliferation of breast cancer SK-BR-3 cells. MethodsSK-BR-3 cells were treated with different concentrations (0, 10, 30, 50 μmol/L) of PEITC respectively. The proliferation capacity of SK-BR-3 cells was detected by MTT and BrdU staining methods. The cell apoptosis was detected by TUNEL and flow cytometry methods. The protein and mRNA expressions levels of indexes related apoptosis such as Bcl-2, Bax, and MCL-1 and indexes related endoplasmic reticulum stress (ERS) such as PERK, eIF2α, CHOP, IRE1α, ATF6α were detected by Western blot and quantitative real-time PCR (qRT-PCR), respectively. ResultsCompared with the control group (0 μmol/L PEITC treatment group), the results of MTT and BrdU staining methods showed that the proliferations of SK-BR-3 cells in the 10, 30 and 50 μmol/L PEITC treatment group were decreased in turn with the increase of concentration. The results of TUNEL and flow cytometry methods showed that the apoptosis rates of SK-BR-3 cells in the 10, 30 and 50 μmol/L PEITC treatment group were increased in turn with the increase of concentration. The results of Western blot and qRT-PCR methods showed that the protein and mRNA expression levels of anti-apoptotic indexes (Bcl-2, MCL-1) were decreased with the increase of concentration, while the expression levels of protein and mRNA of the pro-apoptotic index (Bax) and ERS-related indexes (PERK, eIF2α, CHOP, IRE1α, ATF6α) increased with the increase of concentration. ConclusionFrom the preliminary results of this study, PEITC can promote the apoptosis of breast cancer SK-BR-3 cells and inhibit cell proliferation, which might be achieved by regulating the expression levels of indexes related apoptosis and ERS.
ObjectiveTo study the effects of the new small molecular oxygen free radical scavenger Tempol on the survival and vasculogenesis of the long random pattern skin flap (LRPSF) and its mechanism. MethodsEighty-four male Sprague Dawley rats were randomly divided into control and Tempol groups (42 rats in each group). LRPSF of 9 cm×3 cm in size were prepared on the backs of rats in two groups based on the Mcfarlane flap. Rats were administered with Tempol (100 mg/kg) in the Tempol group and with normal saline in the control group by intraperitoneal injection at 15 minutes before operation and at 1-7 day after operation. The rat and the skin flap survival conditions were observed after operation; the survival rate of skin flap was measured, and the vascular structure, vascular volume, and total length of blood vessels were analyzed with Micro-CT three-dimensional imaging after 7 days; HE staining was used to observe the structure of the skin flaps and inflammation, immumohistochemical staining to observe vascular endothelial growth factor (VEGF) expression; water-soluble tetrazolium-1 method was used to measure the content of superoxide dismutase (SOD) and malondialdehyde (MDA), and ELISA to detect the expressions of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) after 1, 3, and 7 days. ResultsAll of rats survived after operation, without hemorrhage, edema, and infection. With the extension of time, necrosis occurred in the distal part of the skin flaps in 2 groups, but the necrosis degree of the Tempol group was lower than that of control group; meanwhile, the blood vessel distribution and continuity were better than those of control group. The skin flaps survival rate, vascular volume, and total length of blood vessels of Tempol group were significantly higher than those of control group after 7 days (P<0.05). The clearer skin flaps structure, lighter inflammation reaction and inflammation cell infiltration, and higher VEGF staining intensity were observed in the Tempol group than the control group after 7 days. There was no significant difference in SOD, MDA, and TNF-α, and IL-6 contents between the 2 groups at immediate after operation. SOD significantly increased, but MDA, TNF-α, and IL-6 contents significantly decreased in the Tempol group when compared with control group after 1, 3, and 7 days (P<0.05). ConclusionTempol can significantly promote the LRPSF survival rates, its mechanism is closely related to the promotion of vasculogenesis and reduction of oxidative stress and inflammation.
Objective To study the changes of receptor activator of nuclear factor-κB ligand (RANKL, an osteoclastogenesis-promoting factor) and osteoprotegerin (OPG, the decoy receptor for RANKL), oxidative stress and bone turnover markers in obstructive sleep apnea-hypopnea syndrome (OSAHS), in order to understand the potential mechanisms underlying bone loss in OSAHS patients. Methods Ninety-eight male patients with OSAHS, confirmed by polysomnography (PSG) study, were enrolled. The patients were divided into mild-moderate groups and severe groups. Forty-two male subjects who were confirmed as not having OSAHS served as the controls. The subjects’ bone mineral density (BMD) and T-score were assessed in lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Blood samples were collected from all subjects for measurement of RANKL, OPG, the bone formation marker bone-specific alkaline phosphatase (BAP), the bone resorption marker tartrate-resistant acid phosphatase-5b (TRAP-5b), total antioxidant capacity (TAOC). Twenty-eight severe OSAHS patients accepted continuous positive airway pressure (CPAP) treatment voluntarily. After 6 months, PSG was conducted, and serum RANKL, OPG, TAOC, TRAP-5b, BAP was measured after six months treatment. Results The BMD, T-score of the femoral neck and the lumbar spine were significantly lower in OSAHS patients as compared to the control group. The level of BAP was significantly decreased in the OSAHS group as compared to the control group, and there was no significant difference in TRAP-5b level between two groups. As compared with the control group, levels of OPG, TAOC and the OPG/RANKL ratio decreased significantly. None of these parameters (BMD, T-score, RANKL, OPG, TRAP-5b, BAP) showed significant difference between patients with mild-moderate and severe OSAHS group. Correlation analysis showed that the apnea hypopnea index and oxygen desaturation index were correlated with TAOC. BAP level was positively correlated with TAOC and lowest pulse oxygen saturation. The serum level of TAOC was lower in the OSAHS group after CPAP therapy, but the levels of RANKL, OPG, TRAP-5b, BAP were not different. As compared with the OSAHS group before CPAP therapy, the BMD of the femoral neck and the lumbar spine were not significant difference. Conclusions In patients with OSAHS, the oxidative stress response is enhanced, and imbalance of OPG/RANKL is shifted, which participates in the occurrence of osteoporosis. The oxidative stress injury of severe OSAHS patients was relieved after non-invasive ventilation treatment, but the effect of oxidative stress response on bone metabolism still needs further evaluation.
Objective To investigate the relationship among rats′ stress ulcer and gastric acid, prostaglandin (PGs) and adrenocorticotropin (ACTH) and to probe the pathogenesis, prophylaxis and therapy. Methods Rats′ stress ulcer model was made by cold water soaking and was properly treated with drugs such as hyoscine, dexamethasone, ranitidine and losec. The amount and pH of gastric juice, change of gastric mucosa and PGs and ACTH of blood were determined. Results After rats were fasted for 24 hours a little gastric juice was aspirated. After cold water soaking of rats gastric juice was increased with the pH decreased, there was gastric mucosal bleeding, blood PGs was decreased and ACTH was increased. These suggest that on stress gastric mucosa bleeding is related with decreased gastric juice pH, decreased PGs and increase ACTH.Conclusion To control stress ulcer, pH of gastric juice and amount of PGs should be increased. Losec can increase gastric juice pH, so losec is the first choice to control stress ulcer.
Objective To explore the change of gene expression of stress activated protein kinase (SAPK) and its upstream signalregulated molecule ——mitogen activated protein kinases(MAPKs) (MKK4 and MKK7) in hypertrophic scar and autocontrol normal skin. Methods The total RNA was isolated from 8 hypertrophic scars and 8 auto-control skin, and then mRNA was purified. The gene expressions of MKK4, MKK7 and SAPK were examined with reverse transcriptionpolymerase chain reaction(RT-PCR) method. Results In hypertrophic scar, both MKK7 and SAPK genes weakly expressed. In auto-control skin, the expression of these 2 genes was significantly elevated in comparison with hypertrophic scar (Plt;0.01). The expression levelsof these 2 genes were 1.5 times and 2.6 times as long as those of hypertrophic scar, respectively. Gene expression of MKK4 had no significant difference between autocontrol skin and hypertrophic scar (Pgt;0.05). Conclusion Decreased gene expression of MKK7 and SAPK which results in reducing cell apoptosis might be one of the mechanisms for controlling the formation of hypertrophic scar.
目的:观察阿托伐他汀对抗糖尿病肾病患者肾氧化损伤作用。方法:56例糖尿病肾病患者随即分为对照组和阿托伐他汀组。对照组给予降糖、降压等治疗,阿托伐他汀组则在对照组治疗基础上加用阿托伐他汀10 mg/d,疗程共12周。检测两组患者治疗前后FBG、BUN、Scr、尿微量白蛋白以及血脂、血清SOD和MDA水平。结果:12周后两组患者FBG、BUN、Scr、尿微量白蛋白均较治疗前下降;与治疗前相比,阿托伐他汀组患者血脂水平较治疗前明显改善,同时患者血清SOD活性增,MDA含量下降,二者之间的差异具有显著性意义。结论:阿托伐他汀除具有降血脂作用外,还可改善糖尿病肾病患者的氧化应激状态。
ObjectiveTo investigate the systemic stress responses after laparoscopic resection in colorectal cancer patients.MethodsSixty patients were randomized into the laparoscopic resection group (30 cases) and open resection group (30 cases) from October 2001 to September 2002 in our hospital.Analgesic dosages, recovery time of intestinal peristalsis, postoperative temperatures, C reactive protein(CRP), IL6 and white blood cell (WBC) counts were recorded after operation. ResultsThe changes of postoperative temperatures and WBC counts showed no significant difference between two groups.But in the laparoscopic resection group, the recovery time of intestinal peristalsis, postoperative analgesic dosages, CRP and IL6 significantly decreased (P＜0.01,P＜0.05).ConclusionCompared with traditional open resection, laparoscopic resection of colorectal cancer can diminish the systemic stress responses and decrease the injury to patients.
Diabetic retinopathy (DR), a neurovascular complication of diabetes, presents a multifaceted pathogenesis that encompasses numerous biological processes and molecular mechanisms. Endoplasmic reticulum stress (ERS) plays a critical role in the maintenance of cellular homeostasis, and diabetic neuro-microangiopathy is driven by high glucose, which activated ERS through the promotion of protein misfolding, oxidative stress, and disturbances in calcium homeostasis. ERS activates the unfolded protein response, thereby influencing the onset and progression of DR through modulating mitochondria-associated endoplasmic reticulum membranes, autophagy, apoptosis, microvascular function, oxidative stress, and inflammation pathways. Currently, the principal interventions against ERS comprise the modulation of the ERS signalling axis and its interactions with associated pathological processes such as autophagy, oxidative stress, and inflammation, through pharmacological and molecular mechanisms. These interventions are directly or indirectly shown to inhibit persistent ERS and are demonstrated to ameliorate DR. With the in-depth study of ERS and the research and development of various drugs for ERS, it is expected to bring novel insights and strategies for DR management in the future.
目的:探讨5·12 四川汶川大地震对系统性红斑狼疮(SLE)病情活动性的影响,以及因地震造成的停药、感染、居住环境恶劣(长期紫外线照射)和创伤后应激障碍(posttraumatic stress disease,PTSD)与病情活动性的相关性。方法:分析41例重灾区(北川、平武、江油、安县)SLE患者地震前后实验室指标和临床表现变化情况,采用Logistic回归分析地震造成停药、感染、居住环境恶劣和PTSD四种因素对SLE病情活动性的影响。结果:41例SLE患者地震后有18例病情活动,其中有27%患者出现关节痛,24%出现颜面红斑,19.5%出现发热,22%合并狼疮肾炎，震后C3水平显著低于震前。震后6例患者感染,13例患者停药,16例患者长期居住于恶劣环境中,11例患者患PTSD。通过Logistic回归分析发现PTSD、停药、居住条件恶劣与地震后SLE患者病情活动相关。结论:地震可使一部分重灾区SLE患者病情出现活动,PTSD、停药、居住条件恶劣与SLE病情活动具有相关性。
Objective To investigate the efficacy of phloretin combined with sodium hyaluronate in preventing postoperative abdominal adhesion formation in rats and its possible mechanisms. Methods Forty rats were randomly divided into five groups, the rats in the sham-operatinon group only underwent open and closed abdominal surgery, and the remaining rats of four groups underwent cecum scratch-and-rub method of modeling to receive different treatments: the rats in the control group and the phloretin group (PHL group) were closed abdominally after modeling, while the rats in the sodium hyaluronate group (HA group) and the phloretin combined with sodium hyaluronate group (PHL+HA group) were closed abdominally by using 2 mL of sodium hyaluronate gel coated with the damaged abdominal wall and the cecum; the postoperative groups treated with phloretin (the PHL and PHL+HA groups) were treated with 2 mL of40 mg/kg phloretin dissolved in 0.5% sodium carboxymethylcellulose by gavage daily, and the rest of the groups were treated with 2 mL of 0.5% sodium carboxymethylcellulose solution by gavage. After general anesthesia, the rats were executed on the 7th day after surgery, and the Nair’s score was used to evaluate the adhesion status of each group on the 7th day after surgery; the adhesive tissue or normal peritoneal tissue were collected (cecum and its opposite side of the peritoneal tissue was collected in the sham-operation group), and immunohistochemistry was performed to evaluate the degree of staining with Nrf2 antibody, HE staining was performed to evaluate the inflammation scores, and Sirius red staining was performed to evaluate the thickness of the collagen fibers, and levels of transforming growth factor β1 (TGF-β1), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Results All rats successfully completed the experiment. Compared with the control group, Nair’s score, inflammation score, expression level of TGF-β1, thickness of collagen fibers in the adherent tissues, and MDA level were significantly lower in the PHL+HA group (P<0.05), but the SOD level and expression lever of Nrf2 were significantly higher in the PHL+HA group (P<0.05). Conclusion Phloretin combined with sodium hyaluronate can prevent the formation of postoperative abdominal adhesions in the rat model, which may be related to reducing inflammation, reducing collagen deposition, activating Nrf2 pathway and inhibiting oxidative stress.