Effect of granulocyte colony-stimulating factor (G-CSF) on chemotherapy-induced oral mucositis

In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intra-arterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n=7) was given G-CSF and group B (n=7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (<2,000/mm³). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm³: group A-1 (n=3) and group A-2 (n=4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis.     

Role of PI3-kinase/Akt signalling pathway in renal function and cell proliferation after renal ischaemia/reperfusion injury in mice

BACKGROUND: PI3K/Akt pathway has been shown to play a critical role in the regulation of mitogenic signalling, apoptosis, cell proliferation and survival in a variety of cells and tissues. The aim of the present study was to investigate the role of PI3K/Akt pathway in the renal ischaemia/reperfusion. METHODS: Four experimental groups, sham-operative mice, vehicle-delivered and wortmannin-treated ischaemic/reperfusion injury mice, wortmannin-treated normal mice were designed to examined serum blood urea nitrogen level, renal injury, proliferating cell nuclear antigen protein and Akt phosphorylation status at 30 min, 90 min, 24 h, 48 h of reperfusion after ischaemic treatment. Wortmannin or its vehicle was given intraperitoneally at 4 h before surgery. Blood urea nitrogen was measured, and immunohistochemistry and western blotting were used to detect the components of PI3K/Akt pathway in the ischaemic/reperfusion injury kidney. RESULTS: PI3-kinase inhibitor wortmannin imposes a deleterious effect on serum blood urea nitrogen level, renal function after renal ischaemia/reperfusion injury in mice. The renal cell proliferation increased after ischaemia/reperfusion injury in mouse, which could be inhibited by wortmannin. Phosphorylation of Akt was increased after ischaemia/reperfusion in the mouse kidney, and reduced by wortmannin administration. CONCLUSION: This primary study suggests that PI3-kinase/Akt signalling pathway play an important role in the regulation of the renal repair after ischaemia/reperfusion injury.     

Metformin decreases testicular damages following ischaemia/reperfusion injury in rats

The effects of metformin on a testicular torsion injury in adolescent rat testis after I/R were evaluated in the present study. Forty adolescent rats were divided into five groups with eight rats per group: a control group; a sham-operated group; an ischaemia group, where torsion was applied for 4 hr and testis was examined immediately after detorsion; an I/R group, where torsion was applied for 4 hr and the testis was examined 4 hr after detorsion; and an I/R + M group, where the metformin (300 mg/kg) administration was added to the identical procedures used for the I/R group. Spermatogenesis, basal membrane integrity and cleaved caspase-3 expression were assessed. The I/R + M group had a significantly higher Johnsen score than the I/R group (7.9 ± 0.1 vs. 7.5 ± 0.2; p < .001; F-value = 14.2). Failure of basal membrane integrity was highest in the ischaemia group (45 ± 5) compared to the other groups (control group, 20 ± 5; sham-operated group, 16.6 ± 2.8), but not different between the I/R + M (31.6 ± 12.5) and the I/R groups (25 ± 3.5). Cleaved caspase-3 expression was highest in the ischaemia group (73.5 ± 0.7), and significantly lower in the I/R + M group (33.4 ± 0.9) than the I/R group (58.5 ± 0.2; p < .05; F-value = 7.6). Metformin decreases testicular damage by exerting protection against the harmful effects of I/R on spermatogenesis and alleviating apoptosis in adolescent rat testis.     

Serine/threonine kinase, Cot/Tpl2, regulates renal cell apoptosis in ischaemia/reperfusion injury

Aim: Cot/Tpl2, a serine/threonine (Ser/Thr) protein kinase, has been classified as a member of the mitogen‐activated protein kinase (MAPK) family, and is known to have a pleiotropic role. Many studies have reported the involvement of Cot/Tpl2, mainly as a member of the Toll‐like receptor (TLR) 4 signalling pathway in lipopolysaccharide (LPS)‐induced tumor necrosis factor‐α (TNF‐α) production. At the same time, it is also related to the caspase‐dependent apoptotic pathway. Thus, the role of Cot/Tpl2 in ischaemia/reperfusion injury (IRI) in which TNF‐α and apoptosis are the major pathogenetic factors was studied. Methods: IRI was induced in wild type (Cot/Tpl2^+/+) mice and in Cot/Tpl2‐deficient (Cot/Tpl2^?/?) mice. The extent of tubular injury and renal function were studied. TNF‐α production, neutrophil infiltration and apoptosis were also compared between the two groups. Results: Cot/Tpl2^?/? mice had preserved renal function compared with wild type mice in IRI. Although Cot/Tpl2 was phosphorylated in IRI and in the cultured tubular epithelial cells (TEC) after stimulation with LPS and hydrogen peroxide, there were no significant differences in terms of TNF‐α production, neutrophil infiltration or MAPK activation between Cot/Tpl2^+/+ and Cot/Tpl2^?/? mice. In contrast, Cot/Tpl2^?/? mice showed obviously reduced terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling positive cells and cleaved caspase‐3 positive cells. Furthermore, Cot/Tpl2‐deficient TECs demonstrated significantly less caspase‐3 activation after hydrogen peroxide stimulation with comparable caspase‐9 activation to wild type TEC. Conclusion: Cot/Tpl2 did not function as a member of MAPK family, but as a promoter of apoptosis in IRI. These results suggest that Cot/Tpl2 could be a possible therapeutic target in IRI.     

Minocycline attenuates testicular damages in a rat model of ischaemia/reperfusion (I/R) injury

Testicular torsion is a serious urological disease leading to testicular damage. This study aimed to assess the effect of minocycline on testicular ischaemia/reperfusion (I/R) injury caused by testicular torsion/detorsion. Male adult Wistar rats (n = 32) were assigned into four groups of sham, I/R, I/R + minocycline and minocycline. I/R injury was induced by two sets of surgical operations, including the rotation of the left testis (720°, counterclockwise), followed by detorsion after 4 hr. The administration of minocycline was carried out 30 min before detorsion and then continued for 8 weeks. At the end of the 8th week, rats were killed and sampling was done. Johnson's score, the height of seminiferous tubule epithelium, the mean seminiferous tubule diameter, as well as biochemical parameters, SOD, GPx and CAT, were significantly enhanced in the I/R + minocycline group compared with the I/R group. The administration of minocycline led to a marked decrease in expression levels of Caspase-3, Bax, IL-1β and TNF-α genes, and a remarkable increase in expression levels of Bcl-2, 3β-HSD and 17β-HSD3 genes compared with the I/R group. Administration of minocycline could also reduce the rate of germ cell apoptosis (TUNEL staining). Hence, minocycline was useful in the management of testicular torsion/detorsion.     

Simultaneous production of granulocyte colony-stimulating factor and parathyroid hormone-related protein in bladder cancer

A case of bladder cancer with simultaneous production of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP) is reported. An 81-year-old male patient was admitted to the Saitama Medical School for treatment of gross hematuria, leukocytosis and hypercalcemia and diagnosed as having advanced bladder cancer. Immediately after a cystectomy was carried out, his white cell count and serum calcium levels returned to normal. However, the tumors recurred locally and the recurrence was accompanied by an increase in the serum G-CSF and PTHrP levels with a recurrent elevation of white cell count and the serum calcium level. The production of G-CSF and PTHrP in the tumor cells was confirmed by immunohistochemistry.     

Effects of amlodipine on ischaemia/reperfusion injury in the rat testis

The aim of this study was to examine the effects of amlodipine (AML) in rat testicular torsion/detorsion damage. In this study, rats were divided into eight groups: (i) sham; (ii) testicular ischaemia, 2 h of ischaemia; (iii) testicular ischaemia/reperfusion (I/R), 2 h of ischaemia followed by 2 h of reperfusion; (iv) ischaemia + AML (5 mg kg^?1) administered 30 min before ischaemia; (v) ischaemia + AML (10 mg kg^?1) administered 30 min before ischaemia; (vi) and (vii) I/R + AML (5 mg kg^?1) and I/R + AML (10 mg kg^?1) administered 1.5 h after the induction of ischaemia, respectively, and at the end of a 2‐h ischaemia period and a 2‐h reperfusion period applied; and (viii) sham + AML (10 mg kg^?1). Significant decreases in levels of superoxide dismutase and glutathione were observed in ischaemia and reperfusion groups when compared with healthy controls. These antioxidant levels increased in AML groups while malondialdehyde levels significantly decreased. While increases in tumour necrosis factor‐alpha and transforming growth factor‐beta levels were found in the torsion and detorsion groups, significant decreases in the levels of these inflammatory cytokines were observed in the treatment groups. These results demonstrate that AML significantly produced protective effects on testis tissue damage that occurs in the torsion/detorsion model via biochemical, histopathological and molecular pathways.     

Sitagliptin protects male albino rats with testicular ischaemia/reperfusion damage: Modulation of VCAM-1 and VEGF-A

Twisting of the spermatic cord is considered a popular problem in the urological field, which may lead to testicular necrosis and male infertility. Sitagliptin, a glucose-lowering agent, proved to have a vindicatory function in myocardial and renal ischaemia/reperfusion (I/R), but its role in testicular I/R has not yet been studied. The current work investigates its capability to recover the testicular I/R injury with shedding more light on the mechanism of its action. Four groups were used: sham, sham pretreated with sitagliptin, I/R and sitagliptin/I/R-pretreated groups. The outcomes proved that I/R significantly decreased the serum testosterone, with a major increase in oxidative, inflammatory and nitrosative stress, along with a reduction in testicular vascular endothelial growth factor-A level with marked germinal cell apoptosis. However, pretreatment with sitagliptin significantly reversed the profound testicular I/R damaging effects, on the basis of its antioxidant, anti-inflammatory and anti-apoptotic activities with the ability of recuperation of the testicular vascularity.     

Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study

What’s known on the subject? and What does the study add? It is well known that erythropoietin (EPO) ameliorates the renal injury induced by ischemia or toxins such as cisplatin and radiocontrast media. Also, epidermal growth factor (EGF) exerts a prophylactic nephroprotective effect against the deleterious consequences of the ischemia/reperfusion (I/R) injury. Nevertheless, the combined effect of both drugs remains to be further investigated. This study examined the protective effects of EPO and EGF alone and in combination against renal I/R injury and showed that EPO alone was more powerful than EGF alone and the combination of both drugs was more protective than each agent alone.

OBJECTIVE

To investigate effects of combination of erythropoietin (EPO) and epidermal growth factor (EGF) on renal ischaemia and on reactive oxygen species in a rat model.

MATERIALS AND METHODS

In all, 90 male Sprague‐Dawley rats were allocated into five groups of 18, designated: Sham; treated with right nephrectomy only; Control, subjected to left renal ischaemia for 45 min with no treatment; EPO‐treated, as the control but with EPO pretreatment; EGF‐treated, as the control but with EGF pretreatment; EPO + EGF‐treated, as the control but with EPO and EGF pretreatment. Renal function, histopathology and malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) levels in kidneys were assessed at 1, 2 and 7 days after ischaemia.

RESULTS

All rats except the controls had a significant improvement in serum creatinine, creatinine clearance and fractional excretion of Na⁺; all three were significantly better in EPO + EGF group than in all other groups Histopathological examination showed marked structural damage in control rats. The tubular damage was least in the EPO + EGF group. The control group had a significant increase in MDA level and a significant decrease in SOD and GSH, while the EPO + EGF group had a marked significant reduction in MDA and increase in GSH and SOD.

CONCLUSION

The protection against ischaemia/reperfusion injury might be maximal when EPO and EGF are administered concomitantly, and their protective effect might be partly due to their antioxidant effects.     

Treatment of neutropenia in a renal transplant recipient with granulocyte colony-stimulating factor

We report the use of granulocyte colony-stimulating factor (G-CSF) in a renal transplant recipient in whom neutropenia developed following a presumed viral infection. G-CSF was successful in producing a rise in neutrophil count which coincided with a resolution of fever; there was no adverse effect on renal function. This is the first use of G-CSF in a paediatric renal transplant recipient, and its use should be considered for the immunosuppressed child with persistent neutropenia. Received December 17, 1996; received in revised form August 7, 1997; accepted August 12, 1997     

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury.

BACKGROUND: Ischaemia/reperfusion is a major cause of acute kidney injury and can result in poor long-term graft function. Although most of the patients with acute kidney injury recover their renal function, significant portion of patients suffer from progressive deterioration of renal function. A persistent inflammatory response might be associated with long-term changes following acute ischaemia/reperfusion. Macrophages are known to infiltrate into tubulointersitium in animal models of chronic kidney disease. However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. We aimed to investigate the role of macrophages on the development of tubulointerstitial fibrosis and functional impairment following acute ischaemia/reperfusion injury by depleting macrophages with liposome clodronate. METHODS: Male Sprague-Dawley rats underwent right nephrectomy and clamping of left renal vascular pedicle or sham operation. Liposome clodronate or phosphate buffered saline was administered for 8 weeks. Biochemical and histological renal damage and gene expression of various cytokines were assessed at 4 and 8 weeks after ischaemia/reperfusion. RESULTS: Ischaemic/reperfusion injury resulted in persistent inflammation and tubulointerstital fibrosis with decreased creatinine clearance and increased urinary albumin excretion at 4 and 8 weeks. Macrophage depletion attenuated those changes. This beneficial effect was accompanied with a decrease in gene expression of inflammatory and profibrotic cytokines. CONCLUSIONS: These results suggest that macrophages play an important role in mediating persistent inflammation and fibrosis after ischaemia/reperfusion leading to a development of chronic kidney disease. Strategies targeting macrophage infiltration or activation can be useful in the prevention of development of chronic kidney disease following ischaemic injury.     

Protective effects of Stevia rebaudiana aqueous extract on experimental unilateral testicular ischaemia/reperfusion injury in rats

This project aimed to examine Stevia rebaudiana aqueous extract protective effects on testicular ischaemia/reperfusion injury of rats. Forty rats were randomly divided into five groups: (1) sham group, (2) torsion/detorsion group, (3 and 4) low and high doses treatment groups received S. rebaudiana extract intraperitoneally 30 min before detorsion by 500 and 1,000 mg/kg respectively, and (5) healthy group received the extract by 1,000 mg/kg. In this study, left testes were rotated 2 hr, reperfusion period took long 5 hr, and then orchiectomy was performed. Histopathological and biochemical evaluations of testicular tissue samples were performed. Histopathologically, sham and healthy groups exhibited normal seminiferous tubules. Germinal cell necrosis, interstitial oedema, haemorrhage and congestion were seen in torsion/detorsion group. Testicular tissues of both treatment groups revealed lower histopathological alterations. Significant higher malondialdehyde level was observed in torsion/detorsion group than sham and healthy groups (p < .05). Compared with torsion/detorsion group, S. rebaudiana extract significantly reduced malondialdehyde level in treatment groups (p < .05). Torsion/detorsion group had significantly lower glutathione peroxidase and superoxide dismutase activities than sham and healthy groups, and these parameters showed significant increase in treatment groups compared with torsion/detorsion group (p < .05). The results revealed S. rebaudiana has this potential to protect the testes from ischaemia/reperfusion injury.     

Overexpression of granulocyte colony-stimulating factor induces severe osteopenia in developing mice that is partially prevented by a diet containing vitamin K2 (menatetrenone)

Mice transgenic for granulocyte colony-stimulating factor (G-CSF) exhibit severe osteopenia with an increase of osteoclast number and acceleration of bone resorption in adult mice. To examine the effect of G-CSF overexpression on developing bone, bone mineral density levels were examined from 4 weeks through 36 weeks after birth. Peak bone mass was observed at around 24 weeks of age irrespective of G-CSF expression. Apparent osteopenia was observed as early as 4 weeks of age without detectable developmental retardation in bone length and skeletal structure. Morphological examination confirmed a reduction of cancellous bone and cortical bone at this early stage of life, indicating that overexpression of G-CSF results in apparent osteopenia in developing mice, similar to that in adult animals. The effect of vitamin K2 (menatetrenone) (MK4) on bone phenotypes during development was then examined. Mice were fed chow containing either 0.05 mg MK-4 per 100 g or 20.0 mg MK-4 per 100 g for 12 weeks as the control and experimental diets, respectively. This treatment did not change bone length, irrespective of the type of mouse or diet. Peripheral quantitative computed tomography (pQCT) revealed an increase of in CT value bone of MK4-treated mice. Taken together, these results indicate that overexpression of G-CSF induces an apparent reduction of bone mass and results in osteopenia in developing mice. The bone reduction was partially restored by feeding the mice MK4, suggesting a choice for treatment on the osteopenia induced by G-CSF.     

Association between elevated plasma granulocyte colony-stimulating factor and the degree of surgical stress in patients undergoing gastrointestinal surgery

To characterize the changes in perioperative plasma granulocyte colony-stimulating factor (G-CSF) and analyze the effect of surgical stress on its kinetics, 41 patients undergoing gastrointestinal surgery with varying degrees of surgical stress were examined. The plasma levels of G-CSF significantly increased immediately after the operation, probably in response to surgical injury. This elevation was much higher in the 15 esophagectomy patients, at 883±300 pg/ml on postoperative day (POD) O, than in the 14 gastrectomy patients, with a value of 233±151 on POD O, (P<0.01) or in the 12 cholecystectomy patients, with a value of 64±41 on POD 1 (P<0.01). These findings led us to conclude that G-CSF levels increase significantly in the immediate postoperative period and are most likely associated with the degree of surgical stress. In addition, we studied the priming effect of G-CSF on polymorphonuclear leukocytes (PMNs). G-CSF enhanced PMN superoxide anion (O^– ₂) production and luminol-dependent chemiluminescence (CL) induced by opsonized zymosan in a dose-dependent manner. A significant enhancement was seen in the G-CSF level (1 ng/ml) which was almost the same as the maximum G-CSF level in the esophagectomy patients. Furthermore, postoperative PMN activation occurred after the elevation of plasma G-CSF. Thus, we propose that elevated G-CSF may act as one of the mediators which activate PMN function postoperatively.     

丹参素拮抗氧化应激所致骨质疏松并通过PI3k/Akt通路减少成骨细胞的凋亡

目的探讨丹参素拮抗醋酸泼尼松所致大鼠骨质疏松的作用机理。方法 60只雌性4月龄大鼠随机分为6组:正常对照组、模型组(醋酸泼尼松5 mg/kg体重)、丹参素高中低剂量组(30 mg/kg体重、20 mg/kg体重、10 mg/kg体重)和对照药白藜芦醇组(5 mg/kg体重)。丹参素组和白藜芦醇组每日先给予模型组同样剂量的醋酸泼尼松,然后给予不同浓度药物处理。连续14w。将成骨细胞MC3T3-E1细胞随机分为A组(正常组)、B组(醋酸泼尼松组)、C组(醋酸泼尼松+丹参素干预组),D组(醋酸泼尼松+丹参素+Ly294002组)。采用双能X线骨密度检测仪检测腰椎及股骨的骨矿物密度(BMD);采用TUNEL原位标记骨质疏松大鼠中骨组织检测细胞凋亡情况;同时采用Western-blot检测细胞凋亡相关蛋白Bax、AIF、cyto-C表达情况;免疫荧光和Western-blot检测成骨细胞MC3T3-E1中PI3/Akt信号通路相关蛋白pAkt表达情况。结果与模型组相比,不同浓度的丹参素和白藜芦醇均能升高BMD值(均P0.05),降低骨质疏松大鼠骨细胞凋亡率(P0.05),抑制凋亡相关蛋白Bax、AIF、cyto-C的表达(均P0.05)。与A组相比,B组和D组成骨细胞凋亡率和凋亡相关蛋白Bax、AIF、cyto-C表达均增高(均P0.05);与B组相比,C组成骨细胞凋亡率和凋亡相关蛋白Bax、AIF、cyto-C表达均明显降低(均P0.05);免疫荧光和Western-blot检测显示C组pAkt表达量与B组相比明显增加(P0.05),具有统计学意义。结论丹参素能够拮抗醋酸泼尼松诱导氧化应激所致骨质疏松大鼠中成骨细胞的凋亡,并且在体外是通过活化PI3k/Akt通路而减少成骨细胞的凋亡。     

Effects of erythropoietin on ischaemia/reperfusion injury in a controlled nonheart beating donor kidney model.

Erythropoietin (EPO) has been shown to have an anti-apoptotic action and has the potential to protect against ischaemia/reperfusion injury. This study investigated the effect of high dose EPO (5000 U), administered as a bolus at the onset of reperfusion and at the onset of cold storage in a model of controlled nonheart beating donors kidneys. Porcine kidneys(n = 6) were subjected to 10min warm ischaemia and preserved as follows: Group 1:16 h Cold storage +2 h Normothermic perfusion (16 h CS + 2 h NP) Group 2:16 h CS + 2 h NP + EPO given at the onset of reperfusion Group 3:18 h CS (static hypothermic storage) Group 4:18 h CS + EPO given at the onset of cold storage Haemodynamic and functional parameters were assessed during 3-h reperfusion using autologous blood. Renal blood flow improved in Groups 1 and 2 vs. Groups 3 and 4 though no difference was noted between Groups 3 and 4 (563 +/- 119 vs. 491 +/- 95 vs. 325 +/- 70 vs. 418 +/- 112, respectively; P = 0.012). Total urine output showed no difference between Groups (271 +/- 172 vs. 359 +/- 184 vs. 302 +/- 21 vs. 421 +/- 88; P = 0.576). Percentage serum creatinine fall at 3 h was significantly better in Groups 1 and 2 vs. Group 3 (64 +/- 17 vs. 60 +/- 11 vs. 44 +/- 13 vs. 52 +/- 8; P = 0.04). Fractional-excretion of sodium was significantly lower for Groups 1 and 2 vs. Group 3 and 4 (17 +/- 14 vs. 18 +/- 9 vs. 49 +/- 21 vs. 45 +/- 16 respectively; P = 0.002). There was significant improvement in oxygen consumption in Groups 2 vs. Groups 3 and 4 (P = 0.037) (39 +/- 10 vs. 46 +/- 10 vs. 24 +/- 12 vs. 24 +/- 7 respectively). EPO added at the time of reperfusion improved oxygen consumption when added to NP in comparison to static hypothermic storage but did not exert any other major benefits.     

Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation

Hypoxia-induced inflammation is the critical pathological feature of acute kidney injury (AKI). Activation of hypoxia-inducible factor (HIF) signaling is considered as a central mechanism of body adapting to hypoxia. Hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 (Roxadustat) is a first-in-class HIF stabilizer for the treatment of patients with renal anemia. The current study aimed to investigate whether FG-4592 could protect against ischemia/reperfusion (I/R)-induced kidney injury via inhibiting inflammation. Here, efficacy of FG-4592 was evaluated in a mice model of I/R-induced AKI. Interestingly, improved renal function and renal tubular injuries, combined with reduced kidney injury molecule-1 were observed in the mice with FG-4592 administration. Meanwhile, inflammation responses in FG-4592-treated mice were also strikingly attenuated, as evidenced by the decreased infiltration of macrophages and neutrophils and down-regulated expression of inflammatory cytokines. In vitro, FG-4592 treatment significantly protected the tubular epithelial cells against hypoxia-induced injury, with suppressed inflammation and cell injuries. In summary, FG-4592 treatment could protect against the I/R-induced kidney injury possibly through diminishing tubular cells injuries and suppression of sequence inflammatory responses. Thus, our findings definitely offered a clinical potential approach in treating AKI.     

血小板活化因子与脑缺血/再灌注损伤

血小板活化因子(plateht-activating factor,PAF)是由体内多种细胞在特定条件下所释放的一种活性强大的内源性介质.PAF在脑缺血,再灌注损伤中含量明显增高,对脑缺血,再灌注损伤的发生和发展可能起着主导作用.PAF的作用是由其特异性受体(一种G蛋白耦联受体)所介导的.PAF受体拮抗剂能通过降低PAF的浓度以及抑制PAF受体活性来减轻其脑损伤效应,从而起到脑保护作用.