Prostaglandin release by slow reacting substance from guinea pig and human lung tissue

Slow reacting substance (SRS) injected into the pulmonary artery released prostaglandin E (PGE) and F_2α (PGF_2α) and the 15-keto-13, 14-dihydro PG metabolites from non-sensitized and ovalbumin sensitized, isolated, perfused guinea pig lungs. PGs were also released from lungs incubated with SRS. Sensitized lungs released more PGs in both types of preparations. Indomethacin inhibited the effect of SRS. Passively sensitized human lung fragments, in parallel to guinea pig lung, released PGE, PGF_2α and the metabolites when incubatted with SRS or antigen. In experiments, SRS and arachidonic acid given intravenously increased the airway insufflation pressure in anesthetized guinea pigs. These effects, but not the action of injected PGF_2α and histamine, were abolished by indomethacin. The results indicate that one of the modes of SRS action is by release of PGs, and are consistent with the hypothesis that PGs are predominantly “secondary” mediators (in the temporal sense) of the antigen-antibody reaction.     

Growth in Coculture Stimulates Metabolism of the Phenylurea Herbicide Isoproturon by Sphingomonas sp. Strain SRS2

Metabolism of the phenylurea herbicide isoproturon by Sphingomonas sp. strain SRS2 was significantly enhanced when the strain was grown in coculture with a soil bacterium (designated strain SRS1). Both members of this consortium were isolated from a highly enriched isoproturon-degrading culture derived from an agricultural soil previously treated regularly with the herbicide. Based on analysis of the 16S rRNA gene, strain SRS1 was assigned to the β-subdivision of the proteobacteria and probably represents a new genus. Strain SRS1 was unable to degrade either isoproturon or its known metabolites 3-(4-isopropylphenyl)-1-methylurea, 3-(4-isopropylphenyl)-urea, or 4-isopropyl-aniline. Pure culture studies indicate that Sphingomonas sp. SRS2 is auxotrophic and requires components supplied by association with other soil bacteria. A specific mixture of amino acids appeared to meet these requirements, and it was shown that methionine was essential for Sphingomonas sp. SRS2. This suggests that strain SRS1 supplies amino acids to Sphingomonas sp. SRS2, thereby leading to rapid metabolism of ¹⁴C-labeled isoproturon to ¹⁴CO₂ and corresponding growth of strain SRS2. Proliferation of strain SRS1 suggests that isoproturon metabolism by Sphingomonas sp. SRS2 provides unknown metabolites or cell debris that supports growth of strain SRS1. The role of strain SRS1 in the consortium was not ubiquitous among soil bacteria; however, the indigenous soil microflora and some strains from culture collections also stimulate isoproturon metabolism by Sphingomonas sp. strain SRS2 to a similar extent.     

Melittin-stimulated arachidonic acid metabolism by cultured malignant human epidermal keratinocytes

Upon melittin stimulation, cultured SCC-13 keratinocytes release prostaglandins E₂, F_2α, 6-keto-F_1α, thromboxane B₂, leukotriene B₄, and 6-sulfido-peptide-containing leukotrienes (SRS) into serum free medium. Release of prostaglandins E₂, F_2α, and SRS, normalized to cell protein, is 3- to 10-fold higher from rapidly growing than confluent cultures. Cells growing with hydrocortisone in the medium produce approximately twice the level of the cyclooxygenase-mediated metabolites PGE₂ and PGF_2α as those without hydrocortisone, but similar levels of the lipoxygenase-mediated metabolite SRS. The results demonstrate the potential utility of squamous carcinoma lines for investigating biochemical pathways of arachidonic acid metabolism in keratinocytes.     

Intravenous SRS-induced increases in tracheal mucous gel layer thickness: Evidence for thromboxane involvement

Intravenous (IV) slow reacting substance (SRS) challenge produces bronchoconstriction that can be reduced by cyclooxygenase inhibitors. This report shows that IV SRC challenge also produces significant increases in tracheal mucous gel thickness and that the increases are inhibited by pretreatment with indomethacin (4 mg/kg, PO) or imidazole (10 mg/kg, IV). The increase in gel thickness is preceded by increases in plasma thromboxane B₂ (TXB₂) levels and the inhibition of gel thickening by imidazole is paralleled by decreases in plasma TXB₂ levels. Aerosolized SRS produces increases in tracheal mucous gel thickness which are not inhibited by either indomethacin or imidazole, but are significantly inhibited by FPL-55712. These findings indicate that SRS acts, not only directly to stimulate mucous secretion but also indirectly through an indomethacin and imidazole sensitive mechanism.     

A truncated FatB resulting from a single nucleotide insertion is responsible for reducing saturated fatty acids in maize seed oil

Key message

We identified a G-nucleotide insertion in a maize FatB responsible for reducing saturated fatty acids through QTL mapping and map-based cloning and developed an allele-specific DNA marker for molecular breeding.

Abstract

Vegetable oils with reduced saturated fatty acids have signficant health benefits. SRS72NE, a Dow AgroSciences proprietory maize inbred line, was found to contain signficantly reduced levels of palmitic acid and total saturated fatty acids in seed oil when compared to other common inbreds. Using F₂ and F₃ populations derived from a cross between SRS72NE and a normal inbred SLN74, we have demonstrated that the reduced saturated fatty acid phenotype in SRS72NE is controlled by a single QTL on chromosome 9 that explains 79.1 % of palmitic acid and 79.6 % total saturated fatty acid variations. The QTL was mapped to an interval of 105 kb that contains one single gene, a type B fatty acyl-ACP thioesterase (ZmFatB; GRMZM5G829544). ZmFatB alleles from SRS72NE and common inbreds were cloned and sequenced. SRS72NE fatb allele contains a single nucleotide (G) insertion in the 6th exon, which creates a premature stop codon 22 base pairs down stream. As a result, ZmFatB protein from SRS72NE is predicted to contain eight altered and 90 deleted amino acids at its C-terminus. Because the affected region is part of the conserved acyl-ACP thioesterase catalytic domain, the truncated ZmFatB in SRS72NE is likely non-functional. We also show that fatb RNA level in SRS72NE is reduced by 4.4-fold when compared to the normal allele SNL74. A high throughput DNA assay capable of differentiating the normal and reduced saturate fatty acid alleles has been developed and can be used for accelerated molecular breeding.     

Sequential conversion of the glutathionyl side chain of slow reacting substance (SRS) to cysteinyl-glycine and cysteine in rat basophilic leukemia cells stimulated with A-23187

In rat basophilic leukemia (RBL-1) cells stimulated with A-23187, the major slow reacting substance (SRS) species contain glutathione, cysteinyl-glycine, or cysteine in their side chains, corresponding or closely related to leukotrienes LTC₄, LTD₄, and LTE₄, respectively.³ Evidence is presented that most of the SRS produced during the first few minutes of stimulation by the ionophore has a glutathionyl side chain which is sequentially converted to cysteinyl-glycine and cysteine.     

The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and rat

The biological actions of pure slow-reacting substance of anaphylaxis (SRS-A) from guinea-pig lung, pure slow-reacting substances (SRS) from rat basophilic leukaemia cells (RBL-1) and synthetic leukotrienes C₄ (LTC₄) and D₄ (LTD₄) have been investigated on lung tissue from guinea pig, rabbit and rat. In the guinea pig, the leukotrienes released cyclo-oxygenase products from the perfused lung and contracted strips of parenchyma. The effects of SRS-A, SRS and LTD₄ were indistinguishable. LTC₄ and LTD₄ had similar actions although LTD₄ was more potent than LTC₄. Indo-methacin (1 μg/ml) inhibited the release of cyclo-oxygenase products from perfused guinea-pig lung and caused a marked reduction in contractions of guinea-pig parenchymal strips (GPP) due to LTC₄ and LTD₄. The residual contraction on the GPP was abolished by FPL 55712 (0.5 – 1.0 μg/ml). It appears, therefore, that a major part of the constrictor actions of LTC₄ and LTD₄ in guinea-pig lung are mediated by myotropic cyclo-oxygenase products, i.e. thromboxane A₂ (TxA₂) and prostaglandins (PGs).In rabbit and rat lung, however, SRS-A, SRS and the leukotrienes were much less potent in contracting parenchymal strips and there was little evidence of the release of cyclo-oxygenase products. FPL 55712 at a concentration of 1 μg/ml failed to antagonise leukotriene-induced contractions.     

Intracranial chordoma: radiosurgery,hypofractionated stereotactic radiotherapy and treatment outcomes

BackgroundThe aim of the study was to assess the results of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy (SRS/SRT) for skull base chordomas.Materials and methodsTwenty-three patients aged 12–75 were treated with SRS/SRT due to skull base chordoma. In 19 patients SRS/SRT was a part of the primary therapy, while in 4, a part of the treatment of recurrence. In 4 patients SRS/SRT was used as a boost after conventional radiotherapy and in 19 cases it was the only irradiation method applied. Patients were irradiated to total dose of 6–35 Gy and median total equivalent dose of 52 Gy.ResultsDuring median follow-up of 39 months, 4 patients died. One-, two- and five-year OS was 95%, 89% and 69%, respectively. In nine patients, progression of the disease was diagnosed during study period. One-, two- and five-year progression free survival (PFS) from the end of radiotherapy was 81%, 59% and 43%, respectively. Radiotherapy was well tolerated and only two patients in our group experienced moderate treatment-related toxicity.ConclusionSRS/SRT alone or in combination with surgery is a safe and effective method of irradiation of patients with skull base chordomas. High EQD₂ is necessary to achieve satisfactory treatment results.     

Intérêt de l’imagerie hybride TEMP/TDM pour la scintigraphie des récepteurs de la somatostatine dans le bilan des tumeurs endocrines gastro-entéro-pancréatiques

In this work, we have evaluated the potential of image fusion and attenuation correction (AC) of SPECT-CT imaging for the assessment of gastro-entero-pancreatic endocrine tumors by somatostatin receptor scintigraphy (SRS).MethodAfter optimisation of acquisition and reconstruction parameters, we have evaluated, in a prospective study, SRS performed over a period of one year. We have compared visual interpretations of planar and tomographic images versus SPECT/CT images to determine if anatomical localisation and diagnostic contributions are improved. In a semi-quantitative analysis of pathological foci, we have measured maximal intensity values (T_max), tumour to background ratios (T/B) and tumour contrasts (Ct) with and without AC.ResultsIn 25 SRS, visual analysis has shown anatomical localisation improvements in 60% of cases (CI95%, 39–79) and diagnostic improvements in 64% of cases (CI95%, 43–82). Doubtful foci proportion changed from 44 to 11%. In the semi-quantitative analysis of 41 pathological foci, Wilcoxon matched-pairs tests showed significantly higher T_max, T/B and Ct values after AC.ConclusionSPECT/CT imaging improves diagnostic quality of SRS thanks to a better foci localisation and a better lesional contrast in the image.     

Feasibility and potential advantages using VMAT in SRS metastasis treatments

BackgroundUtilization of stereotactic radiosurgery (SRS) for brain metastases (BM) has become the technique of choice as opposed to whole brain radiation therapy (WBRT). The aim of this work is to evaluate the feasibility and potential benefits in terms of normal tissue (NT) and dose escalation of volumetric modulated arc therapy (VMAT) in SRS metastasis treatment. A VMAT optimization procedure has therefore been developed for internal dose scaling which minimizes planner dependence.Materials and methodsFive patient-plans incorporating treatment with frame-based SRS with dynamic conformal arc technique (DA) were re-planned for VMAT. The lesions selected were between 4–6 cm³. The same geometry used in the DA plans was maintained for the VMAT cases. A VMAT planning procedure was performed attempting to scale the dose in inner auxiliary volumes, and to explore the potential for dose scaling with this technique. Comparison of dose-volume histogram (DVH) parameters were obtained.ResultsVMAT allows a superior NT sparing plus conformity and dose scaling using the auxiliary volumes. The VMAT results were significantly superior in NT sparing, improving both the V₁₀ and V₁₂ values in all cases, with a 2–3 cm³ saving. In addition, VMAT improves the dose coverage D₉₅ by about 0.5 Gy. The objective of dose escalation was achieved with VMAT with an increment of the Dmean and the Dmedian of about 2 Gy.ConclusionsThis work shows a benefit of VMAT in SRS treatment with significant NT sparing. A VMAT optimization procedure, based on auxiliary inner volumes, has been developed, enabling internal dose escalation.     

CO2-induced ion and fluid transport in human retinal pigment epithelium

In the intact eye, the transition from light to dark alters pH, [Ca²⁺], and [K] in the subretinal space (SRS) separating the photoreceptor outer segments and the apical membrane of the retinal pigment epithelium (RPE). In addition to these changes, oxygen consumption in the retina increases with a concomitant release of CO₂ and H₂O into the SRS. The RPE maintains SRS pH and volume homeostasis by transporting these metabolic byproducts to the choroidal blood supply. In vitro, we mimicked the transition from light to dark by increasing apical bath CO₂ from 5 to 13%; this maneuver decreased cell pH from 7.37 ± 0.05 to 7.14 ± 0.06 (n = 13). Our analysis of native and cultured fetal human RPE shows that the apical membrane is significantly more permeable (≈10-fold; n = 7) to CO₂ than the basolateral membrane, perhaps due to its larger exposed surface area. The limited CO₂ diffusion at the basolateral membrane promotes carbonic anhydrase–mediated HCO₃ transport by a basolateral membrane Na/nHCO₃ cotransporter. The activity of this transporter was increased by elevating apical bath CO₂ and was reduced by dorzolamide. Increasing apical bath CO₂ also increased intracellular Na from 15.7 ± 3.3 to 24.0 ± 5.3 mM (n = 6; P < 0.05) by increasing apical membrane Na uptake. The CO₂-induced acidification also inhibited the basolateral membrane Cl/HCO₃ exchanger and increased net steady-state fluid absorption from 2.8 ± 1.6 to 6.7 ± 2.3 µl × cm⁻² × hr⁻¹ (n = 5; P < 0.05). The present experiments show how the RPE can accommodate the increased retinal production of CO₂ and H₂O in the dark, thus preventing acidosis in the SRS. This homeostatic process would preserve the close anatomical relationship between photoreceptor outer segments and RPE in the dark and light, thus protecting the health of the photoreceptors.     

Growth in coculture stimulates metabolism of the phenylurea herbicide isoproturon by Sphingomonas sp. strain SRS2

Metabolism of the phenylurea herbicide isoproturon by Sphingomonas sp. strain SRS2 was significantly enhanced when the strain was grown in coculture with a soil bacterium (designated strain SRS1). Both members of this consortium were isolated from a highly enriched isoproturon-degrading culture derived from an agricultural soil previously treated regularly with the herbicide. Based on analysis of the 16S rRNA gene, strain SRS1 was assigned to the beta-subdivision of the proteobacteria and probably represents a new genus. Strain SRS1 was unable to degrade either isoproturon or its known metabolites 3-(4-isopropylphenyl)-1-methylurea, 3-(4-isopropylphenyl)-urea, or 4-isopropyl-aniline. Pure culture studies indicate that Sphingomonas sp. SRS2 is auxotrophic and requires components supplied by association with other soil bacteria. A specific mixture of amino acids appeared to meet these requirements, and it was shown that methionine was essential for Sphingomonas sp. SRS2. This suggests that strain SRS1 supplies amino acids to Sphingomonas sp. SRS2, thereby leading to rapid metabolism of (14)C-labeled isoproturon to (14)CO(2) and corresponding growth of strain SRS2. Proliferation of strain SRS1 suggests that isoproturon metabolism by Sphingomonas sp. SRS2 provides unknown metabolites or cell debris that supports growth of strain SRS1. The role of strain SRS1 in the consortium was not ubiquitous among soil bacteria; however, the indigenous soil microflora and some strains from culture collections also stimulate isoproturon metabolism by Sphingomonas sp. strain SRS2 to a similar extent.     

Leukotriene C4 production during hypoxic pulmonary vasoconstriction in isolated rat lungs

Leukotriene inhibitors preferentially inhibit hypoxic pulmonary vasoconstriction in isolated rat lungs. If lipoxygenase products are involved in the hypoxic pressor response they might be produced during acute alveolar hypoxia and a leukotriene inhibitor should block both the vasoconstriction and leukotriene production that occurs in response to hypoxia. We investigated in isolated blood perfused rat lungs whether leukotriene C₄ (LTC₄) could be recovered from whole lung lavage fluid during ongoing hypoxic vasoconstriction. Lung lavage from individual rats had slow reacting substance (SRS)-like myotropic activity by guinea pig ileum bioassay. Pooled lavage (10 lungs)_as analyzed by reverse phase high performance liquid chromatography had an ultraviolet absorbing component at the retention time for LTC₄. At this retention time the element had both LTC₄ immunoreactivitiy by radioimmunoassay, and SRS myotropic activity by bioassay. LTC₄ was not found during normoxic ventilation, during normoxic ventilation after a hypoxic pressor response, or during vasoconstriction elicited by KCL. Diethylcarbamazine citrate, a leukotriene synthesis blocker, concomitantly inhibited the hypoxic vasoconstriction and LTC₄ production. Thus 5-lipoxygenase products may play a role in the sequence of events leading to hypoxic pulmonary vasoconstriction.     

Slow reacting substance (SRS) from ionophore A23187-stimulated peritoneal mast cells of the normal rat. II. Evidence for a precursor role of arachidonic acid and further purification.

The generation of slow reacting substance (SRS) from ionophore A23187-stimulated rat peritoneal mast cells was enhanced by arachidonic acid (AA). This SRS generation was inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA), an acetylenic analogue of AA and an inhibitor of both fatty acid cyclooxygenase and lipoxygenase. Indomethacin, a fatty acid cyclooxgenase inhibitor, had an enhancing effect upon SRS generation. This suggests SRS generation occurred through an ETYA sensitive step--perhaps a lipoxygenase. Radiolabel from [14C]-AA was incorporated into SRS with comigration of radioactivity and bioreactivity in silicic acid and thin layer chromatographies. Upon silicic acid chromatography, the active principle was eluted in the methanol fraction. Two-dimensional thin layer chromatography revealed chromatographic separation from other known spasmogenic substances and phospholipids. Mast cell SRS was found to display physiochemical properties similar to those of rat basophilic leukemia cell SRS, namely: that mast cell SRS generation was 1) enhanced by arachidonic acid; 2) inhibited by ETYA but not by indomethacin; 3) incorporation of [14C]-AA into the active principle; and 4) similar behavior during purification in silicic acid and thin layer chromatographies.     

Pregabalin Attenuates Excitotoxicity in Diabetes

Diabetes can exacerbate seizures and worsen seizure-related brain damage. In the present study, we aimed to determine whether the standard antiepileptic drug pregabalin (PGB) protects against pilocarpine-induced seizures and excitotoxicity in diabetes. Adult male Sprague-Dawley rats were divided into either a streptozotocin (STZ)-induced diabetes group or a normal saline (NS) group. Both groups were further divided into subgroups that were treated intravenously with either PGB (15 mg/kg) or a vehicle; all groups were treated with subcutaneous pilocarpine (60 mg/kg) to induce seizures. To evaluate spontaneous recurrent seizures (SRS), PGB-pretreated rats were fed rat chow containing oral PGB (450 mg) for 28 consecutive days; vehicle-pretreated rats were fed regular chow. SRS frequency was monitored for 2 weeks from post-status epilepticus day 15. We evaluated both acute neuronal loss and chronic mossy fiber sprouting in the CA3 area. In addition, we performed patch clamp recordings to study evoked excitatory postsynaptic currents (eEPSCs) in hippocampal CA1 neurons for both vehicle-treated rats with SRS. Finally, we used an RNA interference knockdown method for Kir6.2 in a hippocampal cell line to evaluate PGB''s effects in the presence of high-dose ATP. We found that compared to vehicle-treated rats, PGB-treated rats showed less severe acute seizure activity, reduced acute neuronal loss, and chronic mossy fiber sprouting. In the vehicle-treated STZ rats, eEPSC amplitude was significantly lower after PGB administration, but glibenclamide reversed this effect. The RNA interference study confirmed that PGB could counteract the ATP-sensitive potassium channel (K_ATP)-closing effect of high-dose ATP. By opening K_ATP, PGB protects against neuronal excitotoxicity, and is therefore a potential antiepileptogenic in diabetes. These findings might help develop a clinical algorithm for treating patients with epilepsy and comorbid metabolic disorders.     

Repeat single-fraction stereotactic radiosurgery for recurrent vestibular schwannoma

BackgroundData are scarce on the efficacy of a second radiosurgery (SRS) treatment of vestibular schwannoma that has progressed following initial treatment with SRS. We sought to report the outcome of our repeat SRS series with long-term imaging follow-up.Materials and methodsWe retrospectively analyzed 6 patients who met the following criteria: Repeat SRS at our institution between 1995 and 2018; solitary unilateral tumor; no evidence of neurofibromatosis; and magnetic resonance (MR) planning for both SRS treatments. All treatments were delivered with a linear accelerator-based system using head frame immobilization. The prescribed dose to the periphery of the tumor was 12.5 Gy in all initial and repeat SRS treatments, except for one repeat treatment to 10 Gy.ResultsFollow-up with MR scan following the second SRS treatment was a median 8.4 years. The tumor control rate (lack of progression) following the second SRS treatment was 83% (5/6). Actuarial 10-year outcomes following repeat SRS were: tumor control, 80%; absolute survival, 80%; and cause-specific survival, 100%. Of the patients with at least minimal hearing retention before initial SRS, none had ipsilateral hearing preservation after initial radiation treatment. Improvement in any pretreatment cranial nerve deficits was not seen. The only permanent grade ≥ 3 toxicity from repeat SRS was a case of infraorbital nerve deficit. No patient developed a stroke, malignant transformation, induced second tumor, or facial nerve deficit.ConclusionThere was excellent overall survival, tumor control, and low morbidity in our series for recurrent vestibular schwannoma submitted to repeat single-fraction SRS, supporting additional studies of this treatment strategy.     

In vitro metabolism of pyriproxyfen by microsomes from susceptible and resistant housefly larvae

Levels of cytochrome P450 and b₅ were investigated in microsomal enzymes of houseflies from the gut and fat body of the third instar larvae of a pyriproxyfen-resistant strain (YPPF) and two pyriproxyfen-susceptible strains (YS and SRS). In comparison to the YS and SRS strains, YPPF microsomes had higher levels of total cytochrome P450s in both the gut and fat body. Furthermore, microsomes from the gut and fat body of YPPF larvae were found to have a much greater ability to hydroxylate aniline than YS larvae. In vitro metabolism studies of pyriproxyfen indicated that the metabolic rates were much higher in both the gut and fat body of YPPF larvae than of YS and SRS larvae. The major metabolites of pyriproxyfen in houseflies were identified to be 4′-OH-pyriproxyfen and 5′-OH-pyriproxyfen. Cytochrome P450 inhibitors, piperonyl butoxide (PB) and 2-propynyl 2,3,6-trichlorophenyl ether (PTPE), decreased the metabolic rates significantly in all three strains. This study confirmed that microsomal cytochrome P450 monooxygenases play an important role in the pyriproxyfen resistance of the housefly. Furthermore, it suggests that the fat body must be as important as the gut for the metabolism of pyriproxyfen in resistant housefly larvae. Arch. Insect Biochem. Physiol. 37:215–224, 1998. © 1998 Wiley-Liss, Inc.     

红景天苷对运动后自由基和能量代谢改变的影响

目的:探讨红景天苷在运动过程中对自由基和能量代谢相关指标的作用,从抗氧化系统、能量代谢系统等方面研究红景天苷抗运动性疲劳的机制。方法:本研究采用小鼠运动模型,40只雄性小鼠随机取分为4组(n=10):红景天苷运动组,红景天苷安静组,运动对照组,安静对照组。红景天苷运动组和安静组两组以150 mg/(kg.d)的红景天苷灌胃给药,运动和安静对照组两组以同样体积蒸馏水灌胃,连续给药2周;末次灌胃30 min后,运动组进行无负重游泳120 min,然后测定与运动性疲劳相关的生化指标。结果:研究结果表明,红景天苷能够提高运动小鼠肝脏内超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)等抗氧化酶活性,降低丙二醛(MDA)含量;红景天苷具有稳定运动小鼠血糖,增加肝、肌糖原储备,防止长时间运动后血糖和肝、肌糖原水平降低的作用;红景天苷可提高运动小鼠血浆总胆固醇(TC)、甘油三酯(TG)及游离脂肪酸(FFA)的水平,有影响不同状态下的脂肪代谢,促进脂肪利用的作用。结论:红景天苷对运动过程中自由基和能量代谢改变的影响是其抗运动性疲劳的机制之一。