Comparative Adverse Effects Of Cox-1 and Cox-2 Inhibitors in Rat Liver: An Experimental Study."

The non-steroidal anti-inflammatory drugs (NSAIDs) do not reverse the disease process, but they provide much needed relief from pain and inflammation by inhibiting cyclooxygenase (COX) enzyme mediating the inflammatory pathway. NSAIDs cause number of death as a result of upper gastrointestinal damage. These agents also have unwanted effects on lower bowel, lungs, kidney and cardiovascular symptom. Coxibs are selective inhibitor of cyclooxygenase (COX)-2 and spares the COX-1 induced side effects i.e. gastric ulceration. Therefore in present study we compared the adverse effects of diclofenac sodium (diclo) a non-selective NSAID and valdecoxib (valde), a selective NSAID attherapeutic and subtherapeutic doses. Histological and biochemical changes of liver were observed. Beside that gross examination of the stomach mucosa for ulceration along lesser curvature too observed. For liver functions we estimated serum aspartate aminotransferase (AST), alknine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP). Experiment was carried out by administration of drugs for period of 30 days. Liver sections of diclo &; valde groups showed histological changes, which were more prominent with therapeutic dose of valde. The biochemical changes, subtherapeutic dose of diclo showed increase in ALP only. On the other hand subtherapeutic dose of valde showed significant changes in AST, high significant changes in LDH &; ALP Whereas therapeutic doses of diclo and valde showed highly significant increase in hepatic biochemical parameters i.e. AST, ALT, ALP, LDH.Thus it may conclude that higher doses of COX-1&;2 inhibitors can lead to acute hepatitis and other hepatic complications.     

Myoglobinuria: evaluation of methods in the clinical diagnosis acute renal failure

Patients with red--brown urine which may be a sign of myoglobinuria, can develop acute renal failure. We assayed serum creatinine, blood urea nitrogen (BUN) and creatine kinase activity in a total of 33 patients of equal groups, A (automobile accident), B (trauma) and C (undergoing rhabdomyolysis). In addition we tested 132 urine samples for the presence of myoglobin using a dipstick assay. Only five patients in group A showed any sign of myoglobinuria with increased creatine kinase activity upto 7 times the normal value but their serum creatinine level and BUN were within the normal range. In contrast, all 22 patients in group B and C showed myoglobinuria and above normal concentrations of serum creatinine and BUN, with significantly increased (p < 0.0001) creatine kinase activity upto 150 times the normal range. Four of the most seriously ill patients in group C developed acute renal failure. Supplementation of routine determinations of serum creatinine and BUN and serum creatine kinase activity with a rapid test for myoglobinuria provides an extra indication of impending renal dysfunction. It may be beneficial in the emergency management of these patients.     

原发性肾病综合征(PNS)患儿血清NEFA/ALB比值的变化

目的:观察初发及缓解原发性肾病综合征(PNS)患儿血清NEFA/ ALB 比值的变化,为临床PNS 的诊断及病情评估提供新指标。方法:对52 例PNS 急性期患儿、34 例PNS 缓解期患儿和50 例健康儿童的血清白蛋白(ALB)、游离脂肪酸(NEFA)、尿素氮(BUN)、尿酸(UA)、肌酐(Scr)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平进行定量分析,并对NEFA/ ALB 比值与其他生化指标进行相关性分析。结果:与正常对照组相比,急性组和缓解组患儿血清ALB、HDL-C 水平均显著降低(P< 0.05),而急性组患儿血清NEFA/ ALB、TC、TG、LDL-C、UA 显著升高(P< 0.05);缓解组患儿仅TG、LDL-C 显著升高(P< 0.05)。与缓解组相比,急性组患儿血清ALB 水平显著降低(P <0.05),而血清NEFA/ ALB、TC、TG、LDL-C、UA、BUN、Scr 水平均显著升高(P< 0.05)。将血清生化指标比较中差异有统计学意义的指标与NEFA/ ALB 比值进行相关分析,结果显示NEFA/ ALB 比值与TC、TG、LDL-C、UA、BUN 呈显著正相关性(P 均<0.05),与ALB 呈显著负相关性(P< 0.05)。多元线性逐步回归分析结果显示,血清NEFA/ ALB 比值与BUN 独立相关(β=0.045,t =1.602,P =0.003)。结论:在PNS 疾病发生和发展过程中,NEFA/ ALB 比值升高预示患儿的肾脏功能损伤加重或肾功能降低,对其进行监测有助于临床病情评估与判断。     

肾动脉钙化增加2型糖尿病肾病大鼠进行性肾功能损伤

目的探讨肾动脉钙化对2型糖尿病肾病大鼠肾功能的影响。方法将大鼠随机分为对照组(CON组)、糖尿病肾病组(DN组)及DN合并肾动脉血管钙化组(DN+VC组)。DN组和DN+VC组大鼠在高脂高糖饮食基础上腹腔注射链脲菌素(STZ)制备2型糖尿病肾病(diabetic nephropathy,DN)大鼠模型,造模成功后DN+VC组肌注维生素D3及尼古丁灌胃,分别于实验第8、12和16周末处死大鼠,用Von Kossa染色观察大鼠肾动脉钙盐沉积,Ca2+试剂盒检测肾动脉钙含量,免疫荧光双染观察肾动脉α-SMA/BMP2表达,荧光定量PCR检测肾动脉BMP2 mRNA水平等判断肾动脉钙化程度。检测大鼠血清尿素氮、肌酐、胱抑素C及24 h尿蛋白水平,HE染色观察肾组织病理改变。结果 DN组及DN+VC组肾动脉的钙盐沉积及钙含量、BMP2蛋白及基因表达均较同时间点CON组明显增加,DN+VC组较DN组增加更明显(P0.05)。DN组和DN+VC组大鼠血清尿素氮、肌酐、胱抑素C及24 h尿蛋白随时间进展逐渐升高,且明显高于同时间点CON组(P0.05)。与DN组相比,DN+VC组大鼠仅胱抑素C水平明显升高(P0.05),24 h尿蛋白量在第16周时明显增加(P0.05)。DN组大鼠肾组织病理损伤呈进行性加重,DN+VC组大鼠的病理改变较DN组明显加重。肾动脉钙含量与血清尿素氮、肌酐、胱抑素C、24 h尿蛋白以及BMP2 mRNA呈正相关(P0.01)。结论肾动脉钙化的发生及严重程度可能参与和促进糖尿病肾病的进展。     

Effects of cyclooxygenase inhibition on bone, tendon, and ligament healing

Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of arachidonic acid to prostaglandins (PGs). PGs play a significant role in bone metabolism in health and disease. Conventional non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXIBs) are widely used in patients with musculoskeletal conditions and as a post-surgical analgesics. Due to their effects on PG synthesis, these drugs have been hypothesized to affect the healing process of bone fractures and orthopedic surgical sites. A variety of experimental models of bone, ligament, and tendon repair have assessed the effects of these selective and non-selective COX inhibitors in animals, but with variable outcomes. At this time, large-scale, robust clinical study data do not exist, limiting the relevant assessment of experimental animal data to humans. Here, we provide a critical review of available data on the role of PGs and the effect of COX inhibitors on bone, tendon, and ligament repair. Collectively, this assessment suggests potential involvement of PGs in the healing process of these tissues via modulation by non-selective NSAIDs and selective COX-2 inhibitors. Received 25 April 2005; returned for revision 9 June 2005; accepted by G. Geisslinger 10 June 2005     

Tolerance of nonsteroidal anti-inflammatory drug-sensitive patients to the highly specific cyclooxygenase 2 inhibitors rofecoxib and valdecoxib.

BACKGROUND: Selective inhibitors of cyclooxygenase 2 (COX-2) are generally tolerated by patients sensitive to nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-1. Valdecoxib is a new sulfonamide-containing COX-2-specific inhibitor indicated for the treatment of acute pain, osteoarthritis, and rheumatoid arthritis. OBJECTIVE: To compare the clinical tolerance to rofecoxib and valdecoxib in patients who previously developed urticaria and angioedema while taking classic NSAIDs. METHODS: Patients with challenge-proven NSAID cutaneous sensitivity were submitted to single-blinded controlled oral challenges with rofecoxib, 50 mg, and valdecoxib, 40 mg. RESULTS: Twenty-eight patients (19 females and 9 males; mean +/- SD age, 28.6 +/- 15.0 years; age range, 10-61 years) participated in this study. Twenty-two (85%) of 26 patients who underwent skin tests were atopic, as demonstrated by a clinical history of rhinitis and/or asthma plus positive immediate-type skin hypersensitivity test results. A previous exclusive cutaneous reaction pattern (urticaria and/or angioedema) had occurred in 10 patients (36%), whereas a mixed pattern of skin and respiratory symptoms had occurred in 18 patients (64%). Twenty patients (71%) were multiple reactors, and 8 patients (28%) were single reactors. In this current study, 2 patients (7%) taking rofecoxib experienced angioedema, and 1 patient (4%) taking valdecoxib experienced urticaria. CONCLUSIONS: Rofecoxib and valdecoxib can be safely used by most NSAID-sensitive patients with cutaneous reactions. Our findings suggest that isolated cross-reactions may occur in these patients, and for this reason, controlled oral provocation may be prudent when prescribing valdecoxib or rofecoxib for patients who have previously had urticaria or angioedema triggered by NSAIDs.     

前列地尔联合缬沙坦对慢性肾小球肾炎患者肾功能指标的影响

目的 观察前列地尔联合缬沙坦治疗慢性肾小球肾炎对患者尿蛋白及肾功能指标的影响。方法 选择2017年5月~2019年4月在我院肾内科选取慢性肾小球肾炎患者78例,按照随机数字表法分为对照组和治疗组,各39例。对照组采用缬沙坦治疗,治疗组在对照组基础上联合前列地尔治疗。比较两组尿素氮（BUN）、血肌酐（Scr）、尿酸（UA）、24h尿蛋白定量及临床疗效。结果 治疗后两组BUN、Scr、UA与24h尿蛋白定量水平均低于治疗前,且治疗组低于对照组,差异有统计学意义（P＜0.05）;治疗组有效率高于对照组,差异有统计学意义（P＜0.05）。结论 前列地尔联合缬沙坦能有助于改善患者BUN、Scr、UA、24h尿蛋白定量水平,从而改善肾功能,提高临床疗效。     

妊娠期高血压综合征肾功能指标异常分析

目的探讨妊娠期肾功能尿素氮(BUN)、肌酐(Cr)和尿酸(UA)各指标异常与妊娠高血压综合征之间的关系。方法采用病例对照研究设计,比较不同程度的妊高征患者血清BUN、Cr和UA水平与正常孕妇之间的差别。结果不同程度妊高征患者和正常血压孕妇之间BUN、Cr和UA水平差异有显著性(P<0.05),尤其是重度妊高征患者指标要显著高于其他组。按照《妇产科学》分组,妊高征妇女Cr和UA指标构成与正常对照组之间差异有显著性(P<0.05),以正常对照组平均水平为界分组,高水平的Cr和UA均可显著增加妊高征的患病风险。结论妊娠妇女应该早期筛查肾功能BUN、Cr和UA等指标,以期早期发现并治疗妊高征。     

Cys-C/Cr不同时Cys-C在糖尿病合并肾损伤中的应用

目的 探讨血清胱抑素C(Cys-C)在糖尿病合并肾损伤诊断中的应用价值.方法 将研究对象分为糖尿病组(98例),其中胱抑素C/肌酐( Cys- C/Cr)正常者(87例)为一组,异常者(11例)为另一组,健康对照组(32例),共三组.三组均检测血清胱抑素C(Cys-C),同时检测血肌酐(Cr)、尿素氮(BUN)、白蛋白(AlB)、尿酸(UA)等项目.结果 各生化指标对糖尿病合并肾功能损伤的检出百分率总体为:Cys- C/Cr正常者:Cys-C＞ Cr＞ BUN＞ AlB,UA.Cys- C/Cr异常者:Cys-C＞AlB＞Cr,BUN＞ UA.结论 在Cys- C/Cr正常及异常时,Cys-C检测均可提高糖尿病合并肾功能损伤的检出率.     

Sevoflurane pretreatment enhance HIF-2α expression in mice after renal ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury often occurs, which is one of the major causes of acute kidney injury, thus increasing in-hospital mortality. HIF-2α has a protective role against ischemia of the kidney. Renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. We hypothesized that underlying mechanism responsible for renal protection from sevoflurane pretreatment involves the upregulation of HIF-2α. Sevoflurane pretreatment were performed on WT and HIF-2α knockout mice before renal ischemia/reperfusion. Levels of blood urea nitrogen (BUN) and serum creatinine (Cr) were determined with a standard clinical automatic analyzer. The left kidneys were taken for morphological examination. Expression of HIF-2α in kidney tissue was examined by western blotting. In WT mice, group I/R injury had significantly higher BUN and Cr levels than group control, whereas group I/R + Sev had significantly lower BUN and Cr levels than group I/R injury. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. In HIF-2α^-/- mice, group I/R + Sev showed much higher BUN and Cr levels and severer histological damage than group I/R and group control. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. Our findings suggested that HIF-2α might contribute to the beneficial effect of sevoflurane in renal ischemia/reperfusion injury.     

Notch通路在大鼠肾脏缺血再灌注损伤TLR4介导的炎症反应中的作用

 目的: 探讨Notch通路对大鼠肾脏缺血再灌注损伤(IRI)中Toll样受体4(TLR4)介导的炎症反应的作用。方法: 雄性SD大鼠75只随机分为假手术组(sham组)、缺血再灌注组(IRI组)和γ-分泌酶抑制剂DAPT干预组(DAPT组)。分别于再灌注6 h、12 h、24 h、48 h、72 h时点观察各组肾脏病理改变,检测血尿素氮(BUN)和血清肌酐(Scr)水平,ELISA检测血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平,免疫组化和Western blot分别检测大鼠肾脏Notch1、TLR4和NF-κB p65蛋白表达水平。结果: 在IRI组,呈现不同程度的以肾小管上皮细胞和间质损伤为主的肾脏病理改变,BUN、Scr及血清炎性因子TNF-α、IL-6含量在各时点均显著高于sham组(P<0.05),而在DAPT干预组,在各时点肾脏病理损伤明显减轻,BUN、Scr和血清TNF-α、IL-6水平均显著低于IRI组(P<0.05)。Notch1、TLR4和NF-κB p65主要表达于肾小管上皮细胞胞质中,在sham组仅有微量表达,在IRI组则有高表达,在各时点表达与sham组相比均显著增强(P<0.05),而在DAPT组,各因子的表达水平在各时点均较IRI组显著降低(P<0.05)。结论: 大鼠肾脏IRI出现显著的肾功能及肾脏病理改变,血清炎性因子TNF-α和IL-6水平升高,Notch1、TLR4及NF-κB p65在肾组织中表达增强;而DAPT可通过抑制Notch1活化和TLR4/NF-κB通路,抑制TLR4所介导的炎症反应,从而发挥肾脏保护作用。     

Effects of cyclooxygenase inhibition on the gastrointestinal tract

Cyclooxygenase (COX) is a rate-limiting enzyme that catalyzes the conversion of arachidonic acid, an essential fatty acid present in cell membrane phospholipids and liberated by phospholipase, into prostaglandins (PGs) and prostanoids. COX has two distinct membrane-anchored isoenzymes; COX-1 and COX-2. COX-1 is a constitutively expressed and found in most normal body tissues; COX-2 is expressed in normal tissues at low levels and is highly induced by pro-inflammatory mediators in the setting of inflammation, injury, and pain. Inhibitors of COX activity include: (1) conventional non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs); (2) selective COX-2 inhibitors (COXIBs); and (3) COX-1 inhibitors. Non-selective NSAIDs, at therapeutic doses, inhibit both COX-1 and COX-2. The anti-inflammatory benefits of these drugs are primarily derived from COX-2 inhibition, while inhibition of COX-1 often elicits gastrointestinal (GI) toxicity. Therefore, COXIBs were developed to provide a selective COX-2 agent, i.e., one, that at fully therapeutic doses demonstrated comparable therapeutic benefit to non-selective NSAIDs, without the attendant COX-1-mediated GI toxicities.In this review, we evaluate available literature describing the pathophysiologic role of cyclooxygenases and the effects of their inhibition in GI system in experimental and domestic animal species.     

Plasma Kallikrein-Kinin system mediates immune-mediated renal injury in trichloroethylene-sensitized mice

Trichloroethylene (TCE) is a major environmental pollutant. An immunological response is a newly-recognized mechanism for TCE-induced kidney damage. However, the role of the plasma kallikrein-kinin system (KKS) in immune-mediated kidney injury has never been examined. This study aimed to explore the role of the key components of the KKS, i.e. plasma kallikrein (PK), bradykinin (BK) and its receptors B1R and B2R, in TCE-induced kidney injury. A mouse model of skin sensitization was used to explore the mechanism of injury with or without a PK inhibitor PKSI. Kidney function was evaluated by measuring blood urea nitrogen (BUN) and creatinine (Cr) in conjunction with histopathologic characterization. Plasma BK was determined by ELISA; Renal C5b-9 membrane attack complex was evaluated by immunohistochemistry. Expression of BK and PK in the kidney was detected by immuno?uorescence. mRNA and protein levels of B1R and B2R were assessed by real-time qPCR and Western blot. As expected, numerous inflammatory cell in?ltration and tubular epithelial cell vacuolar degeneration were observed in TCE-sensitized mice. Moreover, serum BUN and Cr and plasma BK were increased. In addition, deposition of BK, PK and C5b-9 were observed and B1R and B2R mRNA and proteins levels were up-regulated. Pre-treatment with PKSI, a highly selective inhibitor of PK, alleviated TCE-induced renal damage. In addition, PKSI attenuated TCE-induced up-regulation of BK, PK and its receptors and C5b-9. These results provided the first evidence that activation of the KKS contributed to immune-mediated renal injury induced by TCE and also helped to identify the KKS as a potential therapeutic target for mitigating chemical sensitization-induced renal damage.     

Protective effect of dapsone against renal ischemia-reperfusion injury in rat

Abstract

Background: Ischemia/reperfusion can cause injury to tissues and compromise functionality of organs due to inflammatory processes. Significantly, development of these effects in kidney tissue has been a challenging issue that leads to acute renal injury. In this study, anti-inflammatory, anti-oxidative, and protective features of dapsone on kidney ischemia/reperfusion injury were investigated.

Material and methods: Renal ischemia was induced in rats by bilateral renal arteries clamping for 45?min followed by 24?h reperfusion phase. The effects of different doses of dapsone (1, 3, 10?mg/kg) on ischemia/reperfusion injury in kidney tissue were investigated by targeting BUN, Creatinine, LDH, MDA, MPO, IL-1β, TNF-α, and NFκB. In addition histopathological examination was performed by H&E staining method.

Results and discussion: Comparing the findings of this study showed significant reduction in BUN and LDH in 10?mg/kg dapsone received groups, and Cr, MDA, and MPO in 3?mg/kg dapsone received groups. The serum level of TNF-α was significantly decreased with both doses of 3 and 10?mg/kg dapsone. The same results were observed in the serum level of IL-1β and NFκB. Besides, remarkable improvement in histological damages was also observed with dapsone treatment.

Conclusion: These results support the hypothesis that the positive effects of dapsone on the renal ischemia/reperfusion injury are mediated by modulating inflammatory cascades.     

The analysis of nonsteroidal antiinflammatory drug selectivity in prostaglandin G/H synthase (PGHS)-null cells

OBJECTIVES: Nonsteroidal antiinflammatory drugs (NSAIDs) that are more selective for PGHS-2 maintain their antiinflammatory properties but exhibit fewer unfavorable gastrointestinal side effects. To evaluate the usefulness of the murine PGHS-null cell system in analyzing PGHS-2 selective inhibitors, we tested PGHS-2 non-selective NSAIDs and two PGHS-2 specific compounds using either endogenous or exogenous sources of substrate, arachidonic acid. MATERIALS AND METHODS: A whole-cell assay system for testing the efficacy of PGHS isozyme-specific inhibitors using murine PGHS-1 or PGHS-2-null fibroblast cell lines derived from lung tissues of PGHS-2(-/-) and PGHS-(-/-) mice, respectively, was employed. PGHS-1 and PGHS-2 null cell lines were exposed to three widely used NSAIDs, ibuprofen, indomethacin and aspirin, and two PGHS-2 specific inhibitors, MK-966 (rofecoxib) and NS-398. Excess arachidonic acid (AA) was provided externally and internally via calcium ionophore A23187. PGHS-1 and PGHS-2 activity were determined by measuring the prostaglandin E2 production by radioimmunoassay. IC50 and IC80 values of each compound were determined from the reduction of PGE2 levels as a measure of inhibition of existing PGHS isozyme in the PGHS-null cells. RESULTS: In our murine PGHS-null cell systems, both PGHS-1 and PGHS-2 null cells can use both externally provided AA and endogenous, A23187-derived AA. Both NS-398 and MK-966 were potent inhibitors and demonstrated strong selectivity for PGHS-2. Among the non-selective NSAIDs, based on the PGHS-2 IC50/PGHS-1 IC50 ratio ranking, ibuprofen is more selective for PGHS-2 than indomethacin while aspirin is the least selective inhibitor regardless of the arachidonic acid source. Indomethacin and MK-966 IC50 values for PGHS-2 were in the range of 10(-9)-10(-8) M while the IC50 values for aspirin were in the range of 10(-5) M. There were differences in the ranking of indomethacin and ibuprofen when the IC80 ratios were used. CONCLUSION: Here, we report on a whole cell assay system for testing the efficacy of PGHS isozyme-specific inhibitors using murine PGHS-1 or PGHS-2-null cell lines. This system, using cells that express either PGHS-1 or PGHS-2, offers a convenient and reliable method to determine IC50 and IC80 values of the two PGHS isoforms, entirely independent of each other, in the same cell type. The results of our evaluation using a panel of NSAIDs, both PGHS-2 selective and non-selective inhibitors, correlate well with previously published clinical and laboratory data, demonstrating the usefulness of the whole-cell assay system described here.     

组蛋白H3K36me3与缺血再灌注诱导小鼠急性肾损伤的相关性研究

目的:研究组蛋白H3K36三甲基化(H3K36me3)在缺血再灌注(IR)诱导的急性肾损伤(AKI)小鼠肾组织中的表达,分析其与肾组织中N-赖氨酸甲基转移酶SMYD2及肾损伤程度的相关性,为临床治疗IR-AKI提供新的靶点。方法:30只ICR小鼠随机分为IR组(n=15)和假手术组(sham组,n=15),应用微动脉夹夹闭双侧肾蒂45 min构建IR模型,于造模后24 h收取小鼠血清和肾组织标本。生化法检测血尿素氮(BUN)和血清肌酐(SCr);HE染色检测肾组织病理学改变;免疫组织化学(IHC)染色检测肾组织中NGAL和cleaved caspase-3的表达;Western blot检测肾组织NGAL、SMYD2、H3K36me3、p-P53、P53、cleaved caspase-3、Bax、Bcl-2、STAT3、p-STAT3、JNK和p-JNK1/2/3蛋白的水平。应用Pearson相关法分析H3K36me3与肾组织SMYD2及NGAL的相关性。结果:与sham组相比,IR组BUN和SCr水平显著升高(P<0.05);HE染色显示,IR组肾小管上皮细胞水肿、脱落、坏死,刷状缘脱落,管腔内大量细胞碎屑残留;IHC染色显示,IR组肾小管上皮细胞中NGAL和cleaved caspase-3明显增多;Western blot结果显示,IR组NGAL、SMYD2、H3K36me3、p-P53、cleaved caspase-3、Bax、STAT3、p-STAT3、JNK及p-JNK1/2/3蛋白的水平明显上调(P<0.05),Bcl-2蛋白水平明显下调(P<0.05);肾组织H3K36me3同SMYD2和NGAL的水平均呈显著正相关。结论:H3K36me3与IR-AKI小鼠肾损伤程度及肾组织SMYD2均密切相关,H3K36me3表达上调可能与STAT3和JNK信号通路活化共同参与调控IR-AKI的发生发展。     

Combination therapies that inhibit cyclooxygenase-2 and leukotriene synthesis prevent disease in murine collagen induced arthritis

Objective and design:  To determine the effect of combinations of cyclooxygenase (COX) inhibitors and inhibitors of leukotriene (LT) syntheses on collagen induced arthritis (CIA) in mice. Methods:  The CIA model was evaluated for the presence of eicosanoids in the paw tissue. Several selective cyclooxygenase 2 (COX-2) inhibitors or non-selective non-steroidal anti inflammatory drugs (NSAIDs) were evaluated alone or in combination with leukotriene (LT) synthesis inhibitors in the CIA model. Results:  Arthritic paw tissue showed increased levels of prostaglandins and leukotrienes in comparison to normal paws. Analysis of mRNA levels indicated the inducible form of the COX-2 enzyme to be the source of prostaglandins. NSAIDs, COX-2 or leukotriene synthesis inhibitors administered alone in CIA decreased severity but had little effect on disease incidence. However, the combination of selective COX-2 inhibitors with leukotriene synthesis inhibitors produced significant decreases in both incidence and severity, suggesting an additive or synergistic effect. This effect was reversible with removal of drug. Little decrease in incidence was observed with the NSAID/5-LO inhibitor combinations. Conclusions:  These results suggest that the induction of the disease in CIA is mediated by products of the COX-2 enzyme and LTB4 production, and that blockade of both pathways is required to prevent CIA. Received 9 July 2008; returned for revision 20 August 2008; received from final revision 19 September 2008; accepted by J. A. Battista 15 October 2008     

地菍总黄酮对糖尿病肾病大鼠胰岛素抵抗和肾损害的影响

目的 研究地菍总黄酮对糖尿病肾病(diabetic nephropathy,DN)大鼠胰岛素抵抗和肾损害的影响.方法 在60只大鼠中随机选取10只为正常组,剩余50只均经腹腔注射链脲佐菌素STZ建立DN模型,共建模成功43只,选取40只DN大鼠随机均分为4组每组各10只,分别为模型组以及地菍总黄酮低剂量组150 mg/...     

芝麻素对肾性高血压伴高血脂大鼠肾脏的保护作用研究

目的： 观察芝麻素对肾性高血压伴高血脂大鼠肾脏的保护作用。方法：制备两肾一夹型肾性高血压伴高血脂大鼠模型(RHHR)，灌胃给予不同剂量的芝麻素7周后，测定各组血清肌酐（Scr）、血尿素氮（BUN）、24 h 尿蛋白含量（UPE）和肾组织匀浆中抗氧化酶的活性，包括总抗氧化能力（T-AOC）、超氧化物歧化酶（SOD）、总NOS（TNOS）、诱导型NOS（iNOS）、结构型NOS（cNOS）和抑制羟自由基能力及肾组织匀浆中丙二醛（MDA）、过氧化氢（H2O2）及一氧化氮（NO）含量。结果：高、中（100 mg/kg、33 mg/kg）剂量组芝麻素可抑制RHHR大鼠血清Scr、BUN和尿UPE水平升高（P<0.01）。与模型组比较可提高肾组织匀浆NO、cNOS、SOD、T-AOC和抑制羟自由基能力（P<0.01或P<0.05），降低MDA、iNOS 、H2O2（P<0.01或P<0.05）含量。结论：芝麻素对肾性高血压伴高血脂大鼠肾脏具有保护作用，其机制与抗氧化应激、清除自由基和抑制iNOS活性等有关。     

新生儿缺血缺氧性脑病血清肌酸激酶及其同工酶、肾功能和血糖动态改变的临床研究

目的探讨新生儿缺血缺氧性脑病（HIE）时血清肌酸激酶（CK）和心型同工酶（CK—MB）,脑型同工酶（CK—BB）,肾功能（BUN,Cr）及血糖动态变化的意义。方法对2005年1月至2007年10月的66例HIE患儿和50例正常新生儿分别在24h内,第7天采集股静脉血,测血清血中总CK,CK—MB,CK—BB,BUN及Cr,血糖采用末梢血。结果（1）HIE组血清CK,CK—MB,CK—BB,BUN,Cr水平高于对照组（P〈0．05）,均随病情加重而升高,生后24h均达到峰值。（2）中,重度组血清CK,CK—MB,CK—BB,BUN,Cr较对照组比较差异显著（P〈0．01）。（3）入院即刻,12h,24h测血糖,重度HIE组与轻、中度HIE在血糖异常种类上有明显差异（P〈0．01）。第7日查血糖各组无统计学意义。结论（1）HIE血清中CK,CK—MB,CK—BB,BUN及Cr水平与HIE程度有密切相关性。（2）血清BUN及Cr则是肾损伤的可靠指标。（3）轻,中度H1E以低血糖为主,重度HIE以高血糖为主。