Clinical Study of Jinmaitong Composita(复方筋脉通) on Diabetic Peripheral Neuropathy

Ｄｉａｂｅｔｉｃｐｅｒｉｐｈｅｒａｌｎｅｕｒｏｐａｔｈｙ（ＤＮ）ｉｓｏｎｅｏｆｔｈｅｍｏｓｔｃｏｍｍｏｎｄｉａｂｅｔｉｃｃｏｍｐｌｉｃａ ｔｉｏｎｓ．Ｉｔｓｐａｔｈｏｇｅｎｅｓｉｓｉｓｓｔｉｌｌｕｎｃｌｅａｒ,ｓｏｎｏｄｅｆｉｎｉｔｅｌｙｅｆｆｅｃｔｉｖｅｍｅｄｉｃｉｎｅｈａｓｂｅｅｎｆｏｕｎｄ．ＣｌｉｎｉｃａｌｓｙｍｐｔｏｍｓｏｆＤＮｃｏｕｌｄｂｅｓｉｇｎｉｆｉｃａｎｔｌｙｒｅｌｉｅｖｅｄｂｙＪｉｎｍａｉｔｏｎｇｃｏｍｐｏｓｉｔａ（ＪＭＴＣ,复方筋脉通）,ａｔｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅ…     

Nerve Regeneration Should Be Highly Valued in the Treatment of Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy （DPN） is the most common chronic complication of the long-term complications of diabetes, affecting up to 90% of patients during the progress of the disease. Many parts of the nerve system, including the sensory nerves, motor nerves and autonomic nerves, can be affected, leading to various clinical features.     

Experiences in Treating Diabetic Peripheral Neuropathy with Traditional Chinese Medicine

Diabetic peripheral neuropathy （DPN） is a common chronic complication in diabetic patients, closely correlated with the development of the disease and with poorly controlled glucose levels. The common clinical signs show paresthesia, mostly manifesting as multiple peripheral neuritis, such as having a chilly or causalgic feeling, anaesthesia, formication, and pain, etc.     

Effect of Jinmaitong (筋脉通) serum on the proliferation of rat Schwann cells cultured in high glucose medium

Objective:To investigate the effect of Jinmaitong(筋脉通,JMT)serum on the proliferation of rat Schwann cells(SCs)primarily cultured in high glucose medium.Method:SOs were primarily cultured in Dulbecco's minmum essential medium(DMEM control),50 mmol/L glucose medium(50 mmol/L Glu),75 mmol/L glucose medium(75 mmol/L Glu),as well as 50 mmol/L glucose medium,with different concentrations of JMT serum(undiluted,1:2 diluted and 1:8 diluted)and Neurotropin(Ntp), respectively.The proliferation of SCs under different conditions was detected by MTT.Result:SCs grew exuberantly in DMEM within 24-72 h,but slowed down at 96 h.The proliferation of SCs was inhibited in 50 mmol/L Glu and 75 mmol/L Glu after cultures of 48,72 and 96 h,which showed that both were significantly different compared to the control group(P<0.01).The inhibition was more significant in 75 mmol/L Glu than in 50 mmol/L Glu(P<0.05).Spearman's rho analysis revealed that the proliferation of SCs had a negative correlation with the concentration of glucose(r=-0.471,P<0.01).Excluding the time factor,partial correlation showed similar results(r=-0.679,P<0.01).After 48 h,the proliferation of SCs increased significantly in JMT1:2 and Ntp compared with 50 mmol/L Glu(control 0.437±0.019,50 mmol/ L Glu 0.367±0.035,JMT1:2 0.426±0.024,Ntp 0.422±0.013;P<0.01),and there were no statistically significant differences among the JMT groups,the Ntp group and the control group(P>0.05).Conclusions: The proliferation of SCs was inhibited in high glucose medium,and the inhibition was reduced by different concentrations of JMT serum,especially at JMT1:2.     

Xueshuantong for Injection (Lyophilized, 注射用血栓通) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats

Objective: To investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection(Lyophilized, 注射用血栓通, XST) in streptozocin(STZ)-induced diabetic retinopathy(DR) rats. Methods: Diabetes mellitus(DM) model was induced by intraperitoneal(i.p.) injection of STZ(60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups(n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fibrillary acidic protein(GFAP), tumor necrosis factor-α(TNF-α) and intercellular cell adhesion molecule-1(ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product(AGE) and its receptor(RAGE) were investigated. Tight junctions proteins(Zonula occludens-1(ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fibrosis, transforming growth factor-β1(TGF-β1)-Smad2/3 signaling pathway were evaluated at last. Results: There was no significant difference in the body weight and blood glucose level between XST and DM groups(P0.05). Compared with the DM group, XST treatment significantly increased the retinal thickness of rats(P0.05 or P0.01), and suppressed cleaved caspase-3 expression(P0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mR NA expressions of matrix metalloproteinase 2(MMP-2) and MMP-9(P0.05 or P0.01). Moreover, XST significantly reduced the productions of AGE and RAGE proteins in the retina of rats(P0.05 or P0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats(P0.05 or P0.01). XST significantly reduced the levels of α-smooth muscle actin(α-SMA), connective tissue growth factor(CTGF), TGF-β1 and phosphorylation of Smad2/3 protein in rats(P0.05 or P0.01). Conclusions: XST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-β/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.     

Effects of Jinmaitong Capsule (筋脉通胶囊) on Ciliary Neurotrophic Factor in Sciatic Nerves of Diabetes Mellitus Rats

Objective:To study the effects of the Chinese medicine Jinmaitong Capsule(筋脉通胶囊,JMT) on the pathomorphology of sciatic nerves,ciliary neurotrophic factor(CNTF),and the mRNA expressions of CNTF in rats with streptozotocin-induced diabetes mellitus(STZ-DM).Methods:The animal model was established by one time intraperitoneal injection of streptozotocin.The rats were simply divided by random into 5 groups including model group,low-dose JMT group(JL),medium-dose JMT group(JM),high-dose JMT group(JH) and neurotropin group.For each of the above 5 groups,a group of 10 normal Wistar rats matched in body weight,age and gender were set as normal group.Intragastric administrations were started after the animal model established.The JL group were administered with five times the JMT dose recommended for a human adult;the JM group were administered with ten times the JMT dose recommended for a human adult;the JH group were administered with twenty times the JMT dose recommended for a human adult.The neurotropin group was administered with ten times the neurotropin dose recommended for a human adult.All rats were given intragastric administration for 16 weeks and then killed.In the 4th,8th,12th,16th week,body weight and blood glucose level were detected before and after the intervention.The morphologic changes of the sciatic nerves were observed by optical microscope and transmission electron microscope.The CNTFmRNA expressions were detected by real-time fluorescent quantitative polymerase chain protein,and the CNTF protein expressions were detected by immunohistochemical method.Results:The blood glucose levels of the STZ-DM rats were much higher than normal group(P<0.01),and there was no apparent difference between any treatment groups and the model group(P>0.05).Before and after the intervention in the 4th, 8th,12th,16th week,there were no significant differences in the body weight among all the groups(P>0.05). The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons,myelin sheaths,and interstitium.The levels of CNTF and CNTF-mRNA expressions in the STZ-DM rats were both significantly decreased(P<0.01).The sciatic nerves of STZ-DM rats might have pathomorphological changes in axons, myelin sheaths,and interstitium.Conclusion:JMT could improve the pathomorphology of sciatic nerves by increasing CNTF’s and CNTF-mRNA expressions in sciatic nerve tissues,and promote the repair and regeneration of damaged nerve fibers.     

A Clinical Study on Treatment of Diabetic Peripheral Neuropathy with Tang Zhi Min Capsules

Diabetic neuropathy is a diabetic chroniccomplication,which often involves the peripheralnervous system.Statistical data shows that 40 % ofthe patients with a long history of the disease maydevelop peripheral neuropathy.The symptoms andsigns include pain,numbness,abnormal sensation,even myophagism in the extremity,so that the lifequality of the patients is affected seriously.     

Strategies and Methods for the Treatment of Diabetic Neuropathy Using Integrative Chinese and Western Medicine

Diabetic neuropathy （DN） is the most common metabolic neuropathy in clinics, not only in diabetes patients （〉60%）, but also in pre-diabetic （8%） and normal persons （5%）^（1）. Its pathogenesis has not been fully understood up to now. It is generally believed that it is related to the increase in glycation endoproducts （AGEs） caused by hyperglycemia,     

Effects of Mitochondrial Dysfunction via AMPK/PGC-1α Signal Pathway on Pathogenic Mechanism of Diabetic Peripheral Neuropathy and the Protective Effects of Chinese Medicine

Diabetic peripheral neuropathy(DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1α pathway and improving mitochondrial function.     

Clinical Study on the Wrist-Ankle Acupuncture Treatment for 30 Cases of Diabetic Peripheral Neuritis

To study the mechanisms of wrist-ankle acupuncture for prevention and treatment of diabeticperipheral neuritis.Methods:Ninety cases of diabetic peripheral neuritis were randomly divided into 3groups,and treated respectively with wrist-ankle acupuncture,body-acupuncture,and the western routinemedical treatment,with 30 cases in each of the groups;and therapeutic effects and laboratory resultscompared.Results:It is proved that the therapeutic effects of the wrist-ankle acupuncture group and bodyacupuncture group were significantly superior to those of the control group,with no significant differencesbetween the former two groups.Conclusion:Wrist-ankle acupuncture has the actions of improving themetabolisms of blood sugar and blood-lipid,lowering down blood viscosity,and restoring the functions ofperipheral nerve cells,thus giving definite therapeutic effects for diabetic peripheral neuritis.     

Clinical Study of Ziyin Yangxue Tongluo Recipe (滋阴养血通络方)in Treating Diabetic Peripheral Nerve Lesion

Diabetes mellitus(DM)peripheralnerve lesion(PNL)is a common chroniccomplication of DM.Its incidence accountsfor 40％-60％ of DM patients.Since elec-tro-physiological examination was devel-oped,its detective rate has reached as highas around 85％.It is a disease that seri-ously affects the patients quality of life.Therefore,our hospital used Ziyin Yangxue     

Clinical Observation on Treatment of Diabetic Nephropathy by Tangweikang (糖微康) Capsule

Ｄｉａｂｅｔｉｃｎｅｐｈｒｏｐａｔｈｙ (ＤＮ)ｉｓｏｎｅｏｆｔｈｅｃｏｍｍｏｎｃｏｍｐｌｉｃａｔｉｏｎｓｉｎｍｉｃｒｏｖｅｓｓｅｌｓｏｆｄｉａ ｂｅｔｅｓｍｅｌｌｉｔｕｓ (ＤＭ ) .Ａｔｐｒｅｓｅｎｔｔｈｅｒｅｉｓｎｏｉｄｅａｌｔｈｅｒａｐｙｔｏｃｕｒｅｉｔ.     

Drug Development for Treatment of Diabetic Peripheral Neuropathy and Salvianolic Acid A Research（糖尿病外周神经病变防治药物与丹酚酸A 研究）

糖尿病是一种严重影响人民身体健康的疾病之一。糖尿病并发症是严重影响病人生活质量和致死的主要原因。糖尿病并发症常见的严重表现为肾功能衰竭、周围神经病变,视网膜病变,心血管、周围血管、脑血管病的发生和发展。糖尿病并发外周神经病变是常见而且危害严重的病理变化。我国具有慢性并发症的糖尿病患者非常普遍,患病率高,危害严重。在慢性糖尿病并发症患者中,有神经病变者占半数以上,糖尿病并发神经病变成为糖尿病并发症的重要临床表现。
防治糖尿病并发症的药物研究进展非常缓慢,临床用药十分匮乏,现有药物治疗效果不能满足临床治疗要求。临床上应用的口服治疗糖尿病的药物有十余种类型数十种药物,近年来,研发了一批新型的抗糖尿病药物,如胰高血糖素样肽（glucagon-like peptide-1,GLP-1）激动剂、二肽二基酶（dipeptidyl peptidase IV,DPP-4）抑制剂、Na+依赖葡萄糖转运载体（sodium-glucose co-transporters,SGLT-2）抑制剂等,这些新型药物的应用,有效提高了对糖尿病的治疗效果,达到了更好的降低血糖的目的。但是,用于防治糖尿病并发周围神经病变的药物依然缺乏。
丹酚酸A是应用多种分子和细胞水平筛选模型,通过综合评价发现的对糖尿病周围神经病变有显著防治作用的药物。采用糖尿病动物并发周围神经病变模型研究表明,丹酚酸A可显著改善糖尿病模型大鼠坐骨神经传导速度,改善周围神经病变症状。丹酚酸A可降低糖尿病大鼠非酶糖基化终末产物（AGEs）含量,降低nNOS含量,缓解血管反应障碍。丹酚酸A可降低高脂动物血中低密度脂蛋白水平、总胆固醇含量。实验结果显示出丹酚酸A对糖尿病周围神经病变的防治作用。
丹酚酸A 可以通过抑制醛糖还原酶、减轻高糖应激、拮抗氧化应激发挥防治糖尿病并发神经病变作用。作用机制研究结果显示,丹酚酸A可抑制醛糖还原酶活性,减轻神经组织病变,促进病变神经组织的恢复;具有较强的抗氧化作用,抑制氧化应激,可以有效清除高糖诱导产生的自由基,激活AMPK,减轻脂质过氧化损伤;提高组织中Na+-K+-ATP酶活性,促进能量代谢;可改善高糖应激反应,减少AGEs的生成,调整代谢紊乱,提高组织对糖的利用,促进糖脂代谢,从而发挥对神经的营养保护作用,促进受损伤神经的修复。
丹酚酸A可以从多个途径发挥防治糖尿病神经病变的作用,可以有效延缓神经病变的进程,促进病变神经组织的功能恢复,并能够通过调整糖尿病患者血糖和脂质代谢过程,减轻神经病变环境的影响,达到防治糖尿病神经病变和改善神经病变症状的效果。     

Inhibitory Effect of Melatonin on the Growth of H22 Hepatocarcinoma Cells by Inducing Apoptosis

Whether melatonin not only inhibits the growth of H22 hepatocarcinoma cells but also induces apoptosis in vitro was assessed. The anti-proliferative effects of melatonin on tumor cells was observed by MTT assay and tumor cells growth curve assay. And the apoptosis of the cells was studied by acridine orange fluorescence assay and flow eytometry. The cell cycle of the tumor cells was also observed by flow eytometry. It was found that melatonin could significantly inhibit the growth of H22 hepatoeareinoma cells. Incubated with melatonin, ehromatin condensation of the tumor cells was observed by fluorescence microscopy. Compared with control, the percentage of apoptotic cells was increased, and the proportion of G0/S increased but that of G0/M decreased. It was suggested that melatonin could directly inhibit the growth of H22 hepatoearcinoma cells by inducing apoptosis and extending the length of cell cycle of the tumor cells.     

Jiangtang Xiaozhi Recipe (降糖消脂方) Prevents Diabetic Retinopathy in Streptozotocin-Induced Diabetic Rats

Objective:To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe(降糖消脂方,JXR) in streptozotocin(STZ)-induced diabetic rats.Methods:Sprague-Dawley rats were randomly divided into normal control group and diabetic group.Rats in the diabetic group were induced by intraperitoneal administration of STZ(50 mg/kg),and subdivided into 5 groups.Rats in the diabetic control group were given saline;four treatment groups were given metformin(300 mg/kg),JXR(2,4 and 8 g/kg) respectively for 8 weeks,while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle.Body weight and food intake were measured every week.The hypoglycaemic effects were determined by testing fasting blood glucose(FBG) every other week,and hemoglobin A1c(Hb A1c),insulin,and glucagon at the end of the treatment.The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining,and periodic acid-schiff staining.The effects were further evaluated by serum superoxide dismutase(SOD) activity and malondialdehyde(MDA).Results:High-dose JXR significantly reduced FBG and Hb A1 c level at the 8th week of administration(P0.01,P0.05).JXR significantly increased insulin level(P0.05),and decreased glucagon level(P0.05).JXR showed the antioxidant defense with increased SOD activity and decreased MDA contents in diabetic rats.Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups.Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment.Conclusion:JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.     

A Novel Mechanism Underlying the Protective Effect of PDE4 Inhibitor Against Cognitive Impairment：Inhibiting Neuroinflammation through Inducing Autophagy in Microglial Cells

Background：Inhibition of pho sphodiesterase 4 （PDE4） improves the learning and memory abilities in Alzheimer’s disease animal models. The cognition-enhancing effects of PDE4 inhibition involve reduced inflammatory responses in the brain. However,the underlying mechanisms are ill-understood. cAMP induces autophagy,and defi ciency of autophagy leads to elevated inflammatory factors. In the present study,we aimed to investigate the contribution of autophagy to the anti-inflammatory effect of PDE4 inhibitor ROF. Methods：Acidic vesicles were traced by Lysotracker（ LYT） red and acridine orange（ AO） staining. Autophagosomes in BV-2 cells was observed by immunofluorescence staining of microtubule-associated protein 1 light chain 3 （LC3）. Aβ25-35 or lipopolysaccharide （LPS） with ATP were used to activate microglial cells and infl ammasome. Cytokine levels were measured by ELISA method. The levels of pro-infl ammatory factors and essential proteins involved in the formation of autophagosome were detected by Western blotting. Results：ROF increased the level of LC3-II,while the level of p62 was decreased. Enhanced fl uorescent signals were observed in BV-2 cells treated with ROF by AO and LYT red staining. In addition,immunofl uorescence indicated a signifi cant increase in punctate LC3. Both LPS plus ATP and Aβ25-35 enhanced the conversion of procaspase- 1 to cleaved-caspase-1 and increased the production of mature IL-1β. Interestingly,these effects were blocked by the treatment of ROF. Moreover,ROF decreased the apoptosis of neuronal N2a cells in conditioned media from BV-2 microglia. These effects were reversed by inhibition of microglial autophagy. Treatment with ROF also showed enhanced autophagy in mcie treated with LPS. Conclusions：PDE4 inhibitor ROF inhibits infl ammasome activities and reduces the release of IL-1β by inducing autophagy.     

A Novel Mechanism Underlying the Protective Effect of PDE4 Inhibitor Against Cognitive Impairment： Inhibiting Neuroinflammation through Inducing Autophagy in Microglial Cells

Background：Inhibition of phosphodiesterase 4 （PDE4） improves the learning and memory abilities in Alzheimer’s disease animal models. The cognition-enhancing effects of PDE4 inhibition involve reduced inflammatory responses in the brain. However,the underlying mechanisms are ill-understood. cAMP induces autophagy,and defi ciency of autophagy leads to elevated inflammatory factors. In the present study,we aimed to investigate the contribution of autophagy to the anti-inflammatory effect of PDE4 inhibitor ROF. Methods：Acidic vesicles were traced by Lysotracker（ LYT） red and acridine orange（ AO） staining. Autophagosomes in BV-2 cells were observed by immunofluorescence staining of microtubule-associated protein 1 light chain 3 （LC3）. Aβ25-35 or lipopolysaccharide （LPS） with ATP were used to activate microglial cells and infl ammasome. Cytokine levels were measured by ELISA method. The levels of pro-infl ammatory factors and essential proteins involved in the formation of autophagosome were detected by Western blotting. Results：ROF increased the level of LC3-II,while the level of p62 was decreased. Enhanced fl uorescent signals were observed in BV-2 cells treated with ROF by AO and LYT red staining. In addition,immunofl uorescence indicated a significant increase in punctate LC3. Both LPS plus ATP and Aβ25-35 enhanced the conversion ofpro-caspase-1 to cleaved-caspase-1 and increased the production of mature IL-1β. Interestingly,these effects were blocked by the treatment of ROF. Moreover,ROF decreased the apoptosis of neuronal N2a cells in conditioned media from BV-2 microglia. These effects were reversed by inhibition of microglial autophagy. Treatment with ROF also showed enhanced autophagy in mcie treated with LPS.Conclusions：PDE4 inhibitor ROF inhibits infl ammasome activities and reduces the release of IL-1β by inducing autophagy.     

Study on the Protective Effect of Shengmai San(生脉散) on the Myocardium in the Type 2 Diabetic Cardiomyopathy Model Rat

Objective:To study the effect of Shengmai San(生脉散Pulse-activating Powder) in protecting myocardium in the rat of the type 2 diabetic cardiomyopathy(DCM) model.Methods:The DCM rat model was established by combination of insulin resistance induced by a high-fat diet with intraperitoneal injection of high dose streptozotocin(50 mg/kg).And these rat models were randomly divided into three groups:a normal group(n=12,one of them died),a model group(n=15) and a Shengmai San group(treatment group,n=15).The damage of the myocardium was assessed by electrocardiogram at the twelfth week after modeling,and the blood glucose,cholesterol and triglyceride levels were determined;the content of the left cardiac ventricle myocardial collagen was quantified by Masson staining test;the level of myocardial cell apoptosis was detected with TUNEL apoptosis detection kit;the damage extent of the myocardial sub-cellular structures was observed by electron microscopy;the expression levels of cardiac TSP-1(Thrombospondin-1),TGF-β1(Transforming Growth Ffactor-β) and TRB-3(Tribbles homolog 3) proteins were detected by immunohistochemical method;the expression levels of cardiac TSP-1,A-TGF-β1 and L-TGF-β1 proteins were detected by Western blotting;and the expression levels of TSP-1 and TRB-3 mRNAs were detected by real-time quantitative PCR.Results:Compared with the control group,the blood glucose,cholesterol,triglycerides levels in both the model groups and the Shengmai San group were significantly decreased;the myocardial tissue was less damaged and the collagen content was reduced in the Shengmai San group;the myocardial sub-cellular structure was injured to a lesser extent;the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and TSP-1,A-TGF-β1,L-TGF-β1 and chymase were decreased,and the expression levels of TSP-1 mRNA and TRB-3 mRNA were decreased in both the model groups and the Shengmai San group(the latter was better),.Conclusion:Shengmai San can inhibit myocardial fibrosis in the rat of diabetic cardiomyopathy,and significantly delay the formation of diabetic cardiomyopathy in hyperglycemia rats through multiple pathways.     

Shen-Fu Injection(参附注射液) Alleviates Post-resuscitation Myocardial Dysfunction by Up-regulating Expression of Sarcoplasmic Reticulum Ca2~+ -ATPase

Objective: To compare the effect of Shen-Fu Injection(SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca2~+ ATPase 2a(SERCA2a) in a pig model with post-resuscitation myocardial dysfunction. Methods: Ventricular fibrillation(VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation(CPR), all animals were randomly administered a bolus injection of saline placebo(SA group, n=10), SFI(0.8 mg/kg, SFI group, n=10) or epinephrine(20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation(ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase(AC), cyclic adenosine monophosphate(c AMP) and the expressions of β1-adrenoceptor(AR) and SERCA 2a were determined. Results: Cardiac output, left ventricular dp/dt_(max) and negative dp/dt_(max) were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2 a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups(P0.05 or P0.01). Conclusions: The administration of epinephrine during CPR decreased the expression of SERCA2 a and aggravated postresuscitation myocardial function(P0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2 a expression.