尾悬吊模拟失重大鼠肺组织一氧化氮合酶的变化

目的 :研究尾悬吊模拟失重大鼠肺组织一氧化氮合酶 (NOS)的变化。方法 :采用尾悬吊模拟失重 ,分为悬吊 7日和 2 1日及相应对照 4个组 ,每组 10只健康雄性 SD大鼠 ,共 4 0只大鼠。并采用免疫组织化学技术检测肺组织 NOS的表达情况。结果 :同正常对照组相比 ,7日尾悬吊模拟失重大鼠肺组织诱导型一氧化氮合酶(i NOS)的表达水平明显增高 (P<0 .0 5 ) ;2 1日的表达水平仍显著增高 (P<0 .0 5 ) ,同时可见血管内皮细胞随着时间延长阳性数目显著增多 (P<0 .0 1)。结论 :在模拟失重条件下肺组织 i NOS的表达水平增高     

关节镜清理联合透明质酸钠治疗膝骨关节炎的短期疗效

目的探究关节镜下清理术联合透明质酸钠腔内注射治疗早中期膝关节骨关节炎的短期临床效果及血清相关指标的变化。 方法回顾性分析广州中医药大学附属佛山市中医院骨科2017年7月至2019年5月收治的膝关节骨关节炎患者。共有108例纳入本研究,采用随机数字表法分为对照组(n＝54)和观察组(n＝54)。两组患者均接受关节镜下膝关节清理术,对照组术后给予安慰剂关节腔内注射,观察组术后给予透明质酸钠关节腔内注射,治疗时间4周,治疗后随访6个月。比较两组治疗前后的疼痛视觉模拟评分(VAS)、日常生活活动量表(ADL)及Lysholm膝关节评分、血清基质金属蛋白酶(MMP-1)、软骨寡聚基质蛋白(COMP)、白介素-1(IL-1)、一氧化氮(NO)和血沉(ESR)的水平,采用t检验比较两组之间的差异。记录两组并发症情况,采用卡方检验评估两组间差异。 结果治疗6个月后,两组ADL及Lysholm评分较治疗前显著升高,治疗后观察组高于对照组(t＝8.390、11.690,P<0.05)。治疗4周后,两组血清MMP-1、COMP、IL-1、NO、ESR水平和VAS评分较治疗前显著降低,治疗后观察组低于对照组(t＝26.284、4.293、5.023、10.508、5.351、8.701, P<0.05)。治疗4周后,观察组并发症发生率为5.56%,与对照组(16.67%)相比,差异无统计学意义(χ²＝2.352,P>0.05)。 结论关节镜下清理术联合透明质酸钠腔内注射治疗早中期膝关节骨关节炎,能在短期内缓解膝关节疼痛、促进关节功能恢复、减轻炎症反应、改善软骨代谢,但远期效果尚需进一步探索和验证。     

Evaluation of the role of L-arginine on spermatological parameters,seminal plasma nitric oxide levels and arginase enzyme activities in rams

The purpose of this study is to investigate the effects of L-arginine on spermatological parameters, seminal plasma nitric oxide levels and arginase enzyme activities. Fertile rams that are 2–3 years old and weighing 50–60 kg were used as material. The semen was collected by artificial vagina at 1st, 4th, 24th, 48th, 72nd, 96th and 120th hours for the control group before L-arginine administration. For treatment groups, L-arginine was administered intraperitoneally at a dose of 5 mg kg⁻¹ bw⁻¹ and semen was collected at the time point described for the control group. Spermatological characteristics of semen samples (semen volume, pH, sperm motility, concentration and abnormal sperm rate), seminal plasma nitric oxide levels and arginase enzyme activities were determined. Increased seminal plasma nitric oxide level (p < .01), seminal plasma arginase activity (p < .01), semen volume (p < .05), semen mass activity (p < .05), sperm motility (p < .05) and concentration (p < .01) and decreased abnormal sperm rate (p < .05 and p < .01) were observed by L-arginine administration. In conclusion, it may be concluded that L-arginine application in rams during the breeding season may have positive effects on rams' reproductive performance.     

Nitric oxide synthase isoform inhibition before whole body ischemia reperfusion in pigs: Vital or protective?

BACKGROUND: Nitric oxide (NO) is a critical regulator of vascular tone, and signal transduction. NO is produced via three unique synthases (NOS); endothelial (eNOS), and neuronal (nNOS) are both constitutively expressed and inducible (iNOS) produced primarily after stimulation. NO has been implicated during and after ischemia reperfusion injury as both a detrimental and cardioprotective mediator. Since cardiopulmonary resuscitation (CPR) in ventricular fibrillation (VF) is a model of whole body ischemia reperfusion injury, it provides an opportunity to assess the effects of NO from the three NOS isoforms. OBJECTIVE: To determine the differential role of nitric oxide synthase isoforms inhibition in ventricular fibrillation CPR and investigate whether inhibition of the NOS isoforms afford any cardioprotection in this model. METHODS: Thirty-two pigs, weight range 25-35 kg, were assigned to four groups of eight animals each. The animals were randomized to receive (1) N(G)-nitro-L-arginine methyl ester (LNAME), a non-selective endothelial nitric oxide synthase inhibitor, (2) 1-(2-trifluoromethylphenyl) imidazole (TRIM), a selective neuronal NOS inhibitor, (3) aminoguanidine (AMINOG), a selective inducible NOS inhibitor or (4) saline control (Control) in equal volumes, 30 min before induction of ventricular fibrillation (VF). After 3 min VF with no intervention, the animals received standard chest compressions using an automated chest compression device (Thumper) for 15 min. After 18 min of VF, single doses of vasopressin and bicarbonate were given and defibrillation attempted. Hemodynamics, regional blood flows, and echocardiography and were performed, before and after drug infusion, during CPR, and after return of spontaneous circulation (ROSC). RESULTS: ROSC for 3 h occurred in 5/8 (63%), 1/8 (13%), 0/8 (0%), and 6/8 (75%) in Control, LNAME, TRIM, and AMINOG treated animals, respectively. After infusion of LNAME, there was a significant increase from baseline in blood pressure [127+/-6 mmHg versus 169+/-3 mmHg, p<0.002] and coronary perfusion pressure [119+/-6 mmHg versus 149+/-6 mmHg, p<0.003]. During CPR, there were no differences among groups in hemodynamics or regional blood flow. In surviving animals, AMINOG had significantly better myocardial function (left ventricular ejection fraction, fractional shortening, and wall motion score index) than control or LNAME treated animals, and attenuated the post-resuscitation hyperemic response in heart and brain. CONCLUSIONS: Intact basal nNOS activity is vital for survival from whole body ischemia reperfusion injury. iNOS inhibition prior to ischemia reperfusion, protects myocardial function after ROSC and decreases myocardial and brain hyperemic response after ROSC.     

Inhibitory Effects of Ginsenoside-Rb2 on Nicotinic Stimulation-Evoked Catecholamine Secretion

The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 (3~30 µM), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 (10 µM) also time-dependently inhibited the CA secretion evoked by DMPP (100 µM, a selective neuronal nicotinic receptor agonist) and high K⁺ (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 (50 µg/mL), the secretory responses of CA evoked by veratridine (a selective Na⁺ channel activator (50 µM), Bay-K-8644 (an L-type dihydropyridine Ca²⁺ channel activator, 10 µM), and cyclopiazonic acid (a cytoplasmic Ca²⁺-ATPase inhibitor, 10 µM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rb2 (10 µM) and L-NAME (an inhibitor of NO synthase, 30 µM), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 (10 µM) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 is mediated by inhibiting both the influx of Ca²⁺ and Na⁺ into the adrenomedullary chromaffin cells and also by suppressing the release of Ca²⁺ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade.     

Effect of ammonium pyrrolidine dithiocarbamate (PDTC) on NF-κB activation and CYP2E1 content of rats with immunological liver injury

Context: Ammonium pyrrolidine dithiocarbamate (PDTC) is a potent inhibitor of nuclear factor-κB (NF-κB). Recent studies have shown that NF-κB plays an essential role in the regulation of genes whose products are involved in the pathogenesis of immunological liver injury.

Objective: To study the function of NF-κB in immunological liver injury of rat model and its effect on CYP2E1 content and metabolic activity.

Materials and methods: The present study investigated the effect of passivating NF-κB activation on CYP2E1 using Bacillus calmette Guérin (BCG)-induced immunological liver injury in Sprague–Dawley rats measured in terms of enzyme levels. The degree of hepatic injury of rats was measured by using biochemical parameters, hepatic tissue pathological changes, and physiological parameters. Protein localization of liver NF-κB was detected by immunohistochemical assay. Western blot analysis was used to detect the protein expression of NF-κB, IκBα, iNOS, and CYP2E1. The content of CYP2E1 of homogenate in the rat liver was detected by ELISA assay and the enzyme kinetics of CYP2E1 probe drug chlorzoxazone was evaluated by high-performance liquid chromatography (HPLC) assay.

Results: The results showed that BCG-pretreatment (125?mg/kg) significantly (p?p?in vivo. Moreover, PDTC (ED₅₀: 76?mg/kg) dose dependently inhibited down-regulation of CYP2E1 (p?Conclusion: Passivation of NF-κB can inhibit the down-regulation of CYP2E1 and iNOS to induce in rat liver tissue with immunological liver injury; NF-κB may be involved in the CYP2E1 regulation through iNOS.     

The Role of Oxidative Stress in Aseptic Loosening of Total Hip Arthroplasties

This study investigated the hypothesis that wear particle-induced oxidative stress initiates osteolysis after total hip arthroplasty (THA). Patient radiographs were scored for osteolysis and periprosthetic tissues were immunostained and imaged to quantify polyethylene wear, inflammation, and five osteoinflammatory and oxidative stress-responsive factors. These included high mobility group protein-B1 (HMGB1), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), 4-hydroxynonenal (4-HNE), and nitrotyrosine (NT). The results show wear debris correlated with inflammation, 4-HNE, NT and HMGB1, whereas inflammation only correlated with NT and HMGB1. Similar to wear debris and inflammation, osteolysis correlated with HMGB1. Additionally, osteolysis correlated with COX2 and 4-HNE, but not iNOS or NT. Understanding the involvement of oxidative stress in wear-induced osteolysis will help identify diagnostic biomarkers and therapeutic targets to prevent osteolysis after THA.