Fructose 1,6-diphosphate alleviates myocardial ischemia reperfusion injury in rats through JAK2/STAT3 pathway

Objective: To study the effect of fructose 1,6-diphosphate(FDP) on myocardial ischemia reperfusion injury in rats and its molecular mechanism.Methods: Male SPF SD rats were selected as experimental animals and randomly divided into four groups.Sham group received sham operation, I/R group were made into myocardial ischemia reperfusion injury models, FDP group were made into myocardial ischemia reperfusion injury models and then were given FDP intervention, and FDP+AG490 group were made into myocardial ischemia reperfusion injury models and then were given FDP and JAK2 inhibitor AG490 intervention.Results: CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of I/R group were significantly higher than those of Sham group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissues were significantly lower than those of Sham group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP group were significantly lower than those of I/R group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissue were significantly higher than those of I/R group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP+AG490 group were significantly higher than those of FDP group whereas Bcl-2 protein expression in myocardial tissue was significantly lower than that of FDP group.Conclusion: FDP could reduce the myocardial ischemia reperfusion injury in rats by activating the JAK2/STAT3 pathway.

Repeated febrile convulsions impair hippocampal neurons and cause synaptic damage in immature rats: neuroprotective effect of fructose-1,6-diphosphate

Fructose-1,6-diphosphate is a metabolic intermediate that promotes cell metabolism. We hypothesize that fructose-1,6-diphosphate can protect against neuronal damage induced by febrile convulsions. Hot-water bathing was used to establish a repetitive febrile convulsion model in rats aged 21 days, equivalent to 3–5 years in humans. Ninety minutes before each seizure induction, rats received an intraperitoneal injection of low- or high-dose fructose-1,6-diphosphate（500 or 1,000 mg/kg, respectively）. Low- and high-dose fructose-1,6-diphosphate prolonged the latency and shortened the duration of seizures. Furthermore, high-dose fructose-1,6-diphosphate effectively reduced seizure severity. Transmission electron microscopy revealed that 24 hours after the last seizure, high-dose fructose-1,6-diphosphate reduced mitochondrial swelling, rough endoplasmic reticulum degranulation, Golgi dilation and synaptic cleft size, and increased synaptic active zone length, postsynaptic density thickness, and synaptic interface curvature in the hippocampal CA1 area. The present findings suggest that fructose-1,6-diphosphate is a neuroprotectant against hippocampal neuron and synapse damage induced by repeated febrile convulsion in immature rats.

The Effect of Fructose-1,6-diphosphate and HTK Solution on Protecting Primary Cardiac Muscle Cells of Rat with Cold Preservation

In this study we tried to investigate the effect of fructose-1,6-diphosphate and HTK solution on protecting primary cardiac muscle cells of rat with cold preservation. The primary cardiac muscle cells of rat were cultured in vitro with four preservation solutions respectively: 0.9 % sodium chloride solution (group A), FDP (group B), HTK solution (group C) and a mixture of FDP and HTK solution (group D). The cells were preserved for 6, 8 and 10 h at 0-4 ℃. The values of AST and LDH-L and the Na+-K+ ATPase activity in cardiac muscle cells were detected, and the survival rate of cardiac muscle cells was detected with trypan blue staining. The values of AST and LDH-L in group C and group D were remarkable lower those in group A and group B (P<0.001), while the Na+-K+ ATPase activity and the survival rate of cells in group C and group D were much higher than those in group A and group B (P<0.001). The values of AST and LDH-L after 6 hours in group D decreased much more than those in group C (P<0.01), while the Na+-K+ ATPase activity and the survival rate of cells in group D improved more than those in group C (P<0.01). Both of the HTK solution and the mixture of HTK and FDP solution have an evident effect on protecting the primary cardiac muscle cells of rat in vitro with cold preservation, Compared with the HTK solution, the mixture solution has a better short-term protective effect.

PRODUCTION OF FRUCTOSE-l,6-DIPHOSPHATE(FDP) BY PERMEABILIZED SACCHAROMYCES CEREVISIAE AND A KINETIC MODEL FOR FDP ACCUMULATION

Permeable yeast cells were used in the batch production of fructose-1,6-diphosphate(FDP).The optimum reaction conditions were reported to be:reaction temperature 30℃,tolueneconcentration 8%(V/V),and initial ratio of glucose to inorganic phosphorus(Pi)10:1.Addition ofAMP was found to be very beneficial to the FDP production.A multienzyme system model for FDPaccumulation was developed,in which FDP was regarded as a substrate of phosphor-fructokinase(PFK),to simulate the activation effect of FDP on PFK.The model simulations were in good agree-ment with the experimental data.

Effects of nimodipine and fructose-1,6-diphosphate on cerebral damage in carbon monoxide poisoning mice

Objective To study the dose- and time- dependent protective effects and the synergistic effects of nimodipine (NMDP) and fructose-1,6-diphosphate (FDP) against cerebral damage induced by acute carbon monoxide (CO) poisoning in mice. Methods Male mice were exposed to CO 170 mL/kg, i.p. After CO intraperitonealy exposure, mortality of mice, change in memory function estimated by passive avoidance test, the pathomorphologic observation of brain tissue slices, as well as changes of activities of monoamine oxidase (MAO)-B and Ca 2+-Mg 2+-ATPase in cerebral tissue were studied. In dose-dependent protective effect study, NMDP (10.6, 5.3, 2.7 mg/kg) and FDP (2.6, 1.3, 0.67 g/kg) was injected ip, respectively 15 min after CO exposure. To study the time-effect relationship of drugs, NMDP (5.3 mg/kg) and FDP (1.3 g/kg) were administered ip respectively 15 minutes, 45 minutes and 120 minutes after CO exposure. The combination of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) was administered ip15 minutes, 45 min and 120 minutes after CO exposure to study the synergism of the two drugs. Results Either NMDP (10.6, 5.3 mg/kg) or FDP (2.6, 1.3 g/kg) administered ip within 15 minutes after CO exposure significantly decreased the impairment of memory function and mortality rate induced by CO, inhibited the decrease of Ca 2+-Mg 2+-ATPase activity, blunted the rising of MAO-B activity and prevented the delayed hippocampal neuronal death in poisoning mice. To our surprise, the combined use of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) within 15 minutes after CO exposure had similar effects to that in NMDP (10.6, 5.3 mg/kg) and FDP (2.6, 1.3 g/kg). Conclusions These results suggest that the impairment of CO on brain can be attenuated if NMDP or FDP are administered sufficiently and quickly as soon as possible after CO exposure and there exists a synergism of FDP and NMDP against CO poisoning damage.

The effect of stunned myocardium on heart function and the protection of fructose－1，6－diphosphate on it

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Protective Effect of Tetrandrine and Fructose-1,6-diphos phate on the Model of Focal Cerebral Ischemia in Rats

The effect of tetrandrine (Tet) on the infarction area and volume of rat brain induced by middle cerebral artery occlusion (MCAO) was investigated. The treatment with Tet 7.5, 12.0 or 15.0 mg·kg 1 , or with fructose 1,6 diphosphate (FDP) 200 and 350 mg·kg 1 ip immediately after MCAO, respectively, significantly reduced the infarction area and volume in a dose dependent manner. MK801 and FDP also displayed a protective effect on brain ischemia. A combination of Tet and FDP administered immediately after MCAO, produced a more potent protective effect than those treated with Tet or FDP alone. When Tet or FDP was administered 1 h and 2 h after MCAO, respectively, they could still significantly reduce the infarction area and volume of brain tissue. But, there was no significant protective effect when these two compounds were given 3 h after MCAO.

1,6-二磷酸果糖钙对海兰褐蛋鸡生产性能、蛋品质、血清生化指标和免疫指标的影响

试验旨在研究1,6-二磷酸果糖钙对海兰褐蛋鸡生产性能、蛋品质、血清生化指标和免疫指标的影响。试验选择800只健康、产蛋率相近的380日龄海兰褐蛋鸡,随机分成4组,每组20个重复,每个重复10笼,每笼1只鸡。对照组、低剂量组、中剂量组和高剂量组分别在基础日粮中添加0mg/kg、100mg/kg、200mg/kg和300mg/kg1,6-二磷酸果糖钙,进行为期9周的试验。结果显示:与对照组相比,中、高剂量组产蛋率显著提高(P<0.05),且与1,6-二磷酸果糖钙的添加量呈二次曲线关系(P<0.05);低、中和高剂量组破蛋率显著降低(P<0.05)。中、高剂量组蛋黄颜色和蛋壳强度显著提高(P<0.05),蛋壳强度与1,6-二磷酸果糖钙添加量呈二次曲线关系(P=0.024);低、中和高剂量组的蛋壳比例显著提高(P<0.05),且随1,6-二磷酸果糖钙添加量的增加呈线性升高(P=0.034)。低、中和高剂量组谷丙转氨酶活性显著降低(P<0.05);低、中剂量组总胆固醇含量显著降低(P<0.05),且总胆固醇含量与1,6-二磷酸果糖钙添加量呈二次曲线关系(P=0.004);中、高剂量组高密度脂蛋白含量显著提高(P<0.05);中剂量组低密度脂蛋白含量显著降低(P<0.05),且低密度脂蛋白含量与1,6-二磷酸果糖钙添加量呈二次曲线关系(P=0.036)。低、中和高剂量组的IgM和IgA含量均显著增加(P<0.05),其中IgA含量随1,6-二磷酸果糖钙添加量的增加呈线性升高(P=0.047)。分别对产蛋率、蛋壳强度、总胆固醇含量和低密度脂蛋白含量进行二次曲线方程拟合表明,当1,6-二磷酸果糖钙添加量分别为179、186、243和268mg/kg时,产蛋率、蛋壳强度、总胆固醇含量和低密度脂蛋白含量分别达到最佳。研究提示:日粮中添加200和300mg/kg1,6-二磷酸果糖钙较佳,基于产蛋率、蛋壳强度、总胆固醇含量和低密度脂蛋白含量考虑,适宜的1,6-二磷酸果糖钙添加量分别为179、186、243和268mg/kg。

重组人干扰素α2b联合1,6-二磷酸果糖对轮状病毒肠炎患儿胃肠激素及炎症因子水平的影响

目的探究重组人干扰素α2b联合1,6-二磷酸果糖对轮状病毒肠炎患儿的胃肠激素及炎症因子水平的影响。方法前瞻性选取2018年6月—2023年6月邯郸市妇幼保健院接收的100例轮状病毒肠炎患儿,按信封抽签法随机分为单一组和联合组,每组50例。单一组给予重组人干扰素α2b,联合组给予重组人干扰素α2b联合1,6-二磷酸果糖。比较两组症状改善情况和治疗前后的胃肠激素、心肌酶谱、免疫球蛋白及炎症因子水平。结果联合组的退热时间、止吐时间、大便恢复正常时间、脱水纠正时间均低于单一组(P<0.05)。联合组治疗前后胃泌素、胃动素、血管活性肠肽、乳酸脱氢酶、肌酸激酶同工酶MB、肌酸激酶、免疫球蛋白A、免疫球蛋白G、免疫球蛋白M、白细胞介素-17、白细胞介素-35、肿瘤坏死因子-α的差值均高于单一组(P<0.05)。结论重组人干扰素α2b联合1,6-二磷酸果糖对轮状病毒肠炎患儿胃肠激素及炎症因子水平的影响较为显著。

Protective Effects of Sodium Magnesium Fructose Diphosphate on Brain Damage of Rats Subjected to Focal Cerebral Ischemia and Reperfusion

Objective: To study the effects of sodium magnesiusm fructose diphosphate(FDPM) on brain damage of rats after ischemia-reperfusion. Methods: Rats were subjected to cerebral ischemia-reperfusion induced by inserting a nylon thread into internal carotid artery to block the origin of middle cerebral artery and removing the thread later. FDPM (400 mg·kg -1), fructose-1,6-diphosphate (FDP, 400 mg·kg -1)and magnesium sulfate (MgSO 4, 30 mg·kg -1) were administrated 10 min after the onset of ischemia. Neurological scale, brain infarct area, Malondialdehyde(MDA) content and histopathological changes of brain tissue were studied. Results: FDPM decreased neurological scale, diminished brain infarct area, reduced MDA content and relieved histopathological change of rat brain tissue subjected to ischemia-reperfusion. These effects were more powerful than that of FDP or MgSO 4. Conclusions: It is suggested that FDPM markedly prevented rats against brain damage after cerebral ischemia-reperfusion, and its effect was better than that of FDP or MgSO 4.

1,6-二磷酸果糖和地塞米松对家兔失血性休克缺血再灌注损伤的影响

目的 在家兔失血性休克模型上 ,探讨心肌缺血再灌注损伤机制 ,比较 1,6二磷酸果糖(FDP)和地塞米松 (DXM)对心肌缺血再灌注的保护作用。方法 按照 Wiggers改良法制作兔失血性休克模型。4 8只家兔随机分成 3组 : 组为对照组 ; 组为休克前给药组 (又分为 FDP 、DXM 及 FDP +DXM 3组 ) ; 组为再灌注时给药组 (又分为 FDP 和 DXM 2组 )。观察血浆肌酸激酶 (CK)、心肌肌钙蛋白 I(c Tn I)含量及心肌细胞凋亡情况。结果 各组 CK、c Tn I基础值均无统计学差异 ;与对照组相比 , 组 CK、c Tn I及心肌细胞凋亡指数下降或明显下降 (P<0 .0 5或 P<0 .0 1) ; 组在休克时间点均无统计学意义 ,而再灌注时间点有下降或下降趋势 ,有统计学差异 (P<0 .0 5或 P<0 .0 1) ;与 FDP 和 DXM 组相比 ,FDP 和DXM 组的 CK和 c Tn I上升幅度均有减慢趋势 ,以 FDP组减慢趋势更加明显 ;休克给药组间比较 ,FDP +DXM 组的 CK和 c Tn I上升幅度均减慢。结论 FDP和 DXM对失血性休克引起的缺血再灌注损伤均有保护作用 ,但 FDP仅在缺血开绐给药才能充分发挥其效应 ,二者联合用药对心肌保护有更好的效果。

花生果糖-1,6-二磷酸醛缩酶基因AhFBA1的克隆与表达

以花生品种花育33为试材,根据cDNA文库中已知的果糖-1,6-二磷酸醛缩酶(fructose-1,6-bisphosphate aldolase,FBA)基因全长序列设计引物,通过RT-PCR克隆到该基因,命名为AhFBA1。AhFBA1全长为1489 bp,开放阅读框为1200 bp,编码400个氨基酸。预测该基因编码的蛋白含有Glycolytic保守结构域,可能定位于叶绿体中。蛋白序列比对和进化树分析表明,花生与大豆(Glycine max)、苜蓿(Medicago truncatula)、鹰嘴豆(Cicer arietinum)和菜豆(Phaseolus vulgaris)等豆科植物中的FBA序列相似性最高,亲缘关系最近。荧光定量PCR结果显示,在高盐和干旱胁迫下,AhFBA1在花生叶和根中的表达均受明显诱导,说明该基因可能参与花生对高盐和干旱胁迫的适应性调控;AhFBA1在花生根和叶中均受ABA的明显诱导,说明该基因对花生非生物胁迫的调控可能是依赖ABA的。

1,6-二磷酸果糖对体外循环肺保护的临床实验研究

目的:探讨1,6-二磷酸果糖(FDP)对体外循环(CPB)术后肺保护的效果。方法:将20例二尖瓣瓣膜置换术的风湿性心脏病患者随机分为实验组10例,对照组10例。实验组在体外循环前及体外循环中分别静脉给予FDP200mg/kg,对照组不用FDP。在体外循环前及体外循环后1h分别取左右心房血测定中性粒细胞的跨肺差值;于手术开始前、CPB结束后即刻、CPB结束后1h分别抽取桡动脉血,测定血浆肿瘤坏死因子(TNF-α)、白介素-6(IL-6)、白介素-8(IL-8);分别于体外循环前、停机时,停机后1、8h查动脉血气分析,测呼吸指数(RI)。结果:CPB前两组各项指标差异均无统计学意义,CPB后两组各项指标差异均有统计学意义。结论:FDP对体外循环的肺功能有保护作用。

1,6-二磷酸果糖联合胸腺肽对病毒性心肌炎患儿脑钠肽的影响及疗效观察

目的探讨1,6-二磷酸果糖联合胸腺肽治疗小儿病毒性心肌炎的临床疗效及对脑钠肽的影响。方法选择我院收治的小儿病毒性心肌炎患儿86例为研究对象,随机分为观察组(46例)和对照组(40例),对比分析两组的临床疗效、住院时间、脑钠肽指标的变化及不良反应情况。结果治疗2周后,观察组的显效率及总有效率均明显高于对照组(P<0.05)。观察组平均住院时间较对照组明显缩短(P<0.01)。两组患儿BNP平均水平均较入院时明显降低(P<0.01),但观察组下降更为明显。结论 1,6-二磷酸果糖联合胸腺肽治疗小儿病毒性心肌炎疗效确切,且不良反应少。

依达拉奉和1,6-二磷酸果糖联合应用对全身抗炎作用的影响

目的探讨氧自由基清除剂依达拉奉和能量代谢调节剂1,6-二磷酸果糖(FDP)联合应用对在心肺转流(CPB)下行心脏瓣膜置换手术患者的全身抗炎作用的影响。方法瓣膜置换术患者40例,随机分为依达拉奉组(A组)、FDP组(B组)、联合用药组(C组)和对照组(D组),每组10例。A组将依达拉奉0.5 mg/kg一次性加入CPB预充液中,B组于主动脉阻断前15 min静脉滴注FDP 200 mg/kg,C组为A、B两组药物的联合使用,D组给予等量生理盐水。分别于切皮前(T1)、主动脉阻断前(T2)、CPB停止2 h(T3)6、h(T4)和术后24 h(T5)采集桡动脉血测定血浆超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6I、L-8及IL-10水平,记录心脏复跳情况、心血管活性药物的应用情况及术后24 h创面引流量。结果与D组比较,其他三组能显著减少血浆SOD活性降低的幅度,降低血浆MDA、TNF-αI、L-6I、L-8的升高幅度,增加IL-10的升高幅度(P<0.05),以C组作用最为明显。结论 CPB主动脉阻断前给予依达拉奉或FDP均可减轻自由基反应,抑制全身炎性反应,且两者联合用药作用更明显。

酶法制取1,6-二磷酸果糖的工艺研究

主要研究了不同质壁分离剂对酵母细胞的通透性以及酶活的影响和酶法合成ＦＤＰ的工艺条件。针对糖酵解过程中的各中间代谢产物的理化特性不同，采用阴离子交换树脂分离ＦＤＰ，用酒精—媒晶剂体系结晶ＦＤＰ。产品的总收率和纯度分别为７５％～８０％和９９．５％

油茶果糖-1,6-二磷酸醛缩酶基因(CoFBA4)的分子特征与表达分析

果糖-1，6-二磷酸醛缩酶（fructose-1，6-diphosphatealdolase，FBA，EC4．1．2．13），简称醛缩酶，是糖酵解代谢途径中第4步关键酶，催化果糖-1，6-二磷酸（Fru．1，6-BP）可逆地裂解为磷酸二羟丙酮（DHAP）和3-磷酸甘油醛（G．3-P）（Rutter，1964）。

1,6二磷酸果糖对急性心肌缺血大鼠心功能及内啡肽的影响

结扎大鼠左冠状动脉前降支.造成心肌急性缺血后.引起血液、垂体、部分脑区和心肌组织中β—内啡肽含量的显著上升.并伴有心功能的抑制.急性心肌缺血大鼠给于1.6二磷酸果糖后.可减少β—内啡肽含量的增高.改善心功能.提示1.6二磷酸果糖改善心功能的作用.可能不仅通过改善能量代谢.心肌缺血、缺氧的直接作用.而且还可能通过减少β—内啡肽的过度释放.从而减弱对心功能的抑制.间接地改善心功能.

利用啤酒废酵母生产1,6-二磷酸果糖发酵工艺的研究

啤酒废酵母生产1,6 -二磷酸果糖发酵工艺进行了实验性探讨。正交试验结果表明:发酵液中氯化镁的浓度、pH是1,6 - 二磷酸果糖生产最主要的影响因素。最佳发酵参数为发酵温度37℃,葡萄糖浓度0.4mol/L,磷酸盐浓度0.4mol/L,pH6.5,有机溶剂的加量约6%。发酵液中1,6 -二磷酸果糖的量最高可达70.5mg/mL。

1,6-二磷酸果糖对体外循环期间中性粒细胞的影响

目的 研究体外循环下 1,6 二磷酸果糖 (FDP)对中性粒细胞 (PMNs)活化、释放的影响。方法 2 0例先心病矫正术患者随机分成使用FDP( 2 2 0mg/kg)的观察组 (n =10 )和对照组 (n =10 ) ,动态观察中性粒细胞化学发光 (PMN CL)值、中性粒细胞内髓过氧化物酶 (MPO)及弹性蛋白酶(ELA)活性。结果 ( 1)与阻断主动脉时对比 ,两组各时点PMN CL值均明显升高 (P <0 0 5、P <0 0 1或P <0 0 0 1) ,PMN MPO及ELA活性降低 (P <0 0 5或P <0 0 1) ,化学发光最高值、MPO及ELA活性最低值出现在主动脉开放后 (再灌注 ) 4 5分钟。 ( 2 )与对照组相比 ,在主动脉阻断 3 0分钟、主动脉开放后 (再灌注 ) 4 5分钟及 90分钟 ,观察组PMN CL值降低 ,PMN MPO及ELA活性升高 (P<0 0 5或P <0 0 1)。结论 ( 1)体外循环时PMNs活化并释放多种活性物质 ,且主要发生于主动脉开放后 (再灌注 )早期。 ( 2 )FDP抑制PMNs的活化 ,减轻了PMNs的释放反应。