Objective: To evaluate the clinical efficacy of the Baduanjin exercise prescription on type 2 diabetes with qi and yin deficiency syndrome, and to explore its mechanism. Methods: Randomized method is used in this clinical trial, patients who met the diagnostic criteria of type 2 diabetes mellitus, syndrome of deficiency of qi and yin syndrome were randomly divided into treatment group (the Baduanjin exercise prescription group) and control group (walking exercise group), each group was given corresponding treatment. The main observation index are HOMA-β and HOMA-IR index, fasting and postprandial blood glucose and glycated hemoglobin, TCM syndrome integral, blood lipid levels as a secondary index. The course of treatment was 12 weeks. Results: After treatment, in the treatment group, the HOMA-β increased, the HOMA-IR decreased, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1C) decreased, which was significantly better than that in the control group (P<0.01). The total effective rate of the treatment group was 92.31％, which was better than that of the control group (76.92％, P<0.05). The scores of TCM syndromes and triglycerides were significantly lower than that of the control group (P<0.01). Conclusion: The Baduanjin exercise prescription can reduce the levels of FBG, HbA1C and triglyceride in type 2 diabetes mellitus, thereby improving the function of islet beta cells in type 2 diabetes mellitus.

目的 观察中药复方制剂糖络宁对糖尿病大鼠背根神经节(DRG)线粒体呼吸链氧化呼吸功能、超氧阴离子产生量及膜电位水平的影响.方法 选取SPF级雄性8周SD大鼠80只,随机选择14只为正常组,其余66只大鼠采用链脲佐菌素制作糖尿病大鼠模型;其中61只造模成功大鼠采用随机数字表法分为模型组19只、西药组(α-硫辛酸组)21只、中药组(糖络宁组)21只,共给药8周;给药结束后,检测线粒体呼吸链氧化呼吸功能、超氧阴离子产生量及膜电位水平.结果 与正常组比较,模型组大鼠DRG线粒体呼吸功能明显下降(P＜0.01);与模型组比较,西药组大鼠DRG线粒体呼吸功能明显改善(P＜0.01);与模型组比较,中药组大鼠DRG线粒体呼吸功能未见明显改善(P＞0.05).与正常组比较,模型组大鼠DRG线粒体超氧阴离子明显升高(P＜ 0.01);与模型组比较,中药组、西药组大鼠DRG线粒体超氧阴离子水平明显降低(P＜0.01).与正常组比较,模型组大鼠线粒体膜电位明显下降(P＜0.01);与模型组比较,中药组、西药组大鼠线粒体膜电位明显改善(P＜ 0.01).结论 糖络宁不能改善糖尿病大鼠DRG线粒体氧化呼吸功能,可抑制糖尿病大鼠DRG线粒体超氧阴离子的产生,改善线粒体膜电位水平,这可能是糖络宁治疗糖尿病周围神经病变的作用机制.

Objective:To observe the clinical therapeutic effect and illuminate the mechanism of Tang Shen Ning Granules (TSN) on diabetic kidney disease (DKD).Methods:A multicenter,randomized double-blind and positive drug controlled clinical trial was performed in our study.A total of 250 patients,who had been diagnosed with early stage of DKD,were randomly divided into 2 groups:the normal control group (NC group) and the treatment group (TSN group).Both 2 groups were treated with dietary control and hyperglycemia control.Moreover,the patients of NC group were treated with Losartan (50rg,qd),the patients of TSN group were treated with TSN (8g,bid).The treatment was lasted for 12 weeks.The clinical symptom,UAER,eGFR,SOD and hs-CRP were observed in 2 groups.Results:The total effective rate of TSN group was 86.0％,and the NC group was 58.8％ (P＜0.05).Compared with the NC group,TSN effectively decreased the UAE and relieved the clinical signs of DKD patients (P＜0.01).Compared with the NC group,the level of serum SOD was significantly increased and the level of MDA,hsCRP was significantly decreased in the TSN group (P＜0.05).No adverse reactions and side effects were observed during the trail.Conclusion:TSN is a safe and effective drug for the treatment of early diabetic nephropathy,and its mechanism might be related to the improvement of micro inflammatory state and oxidative stress.

A rapid and accurate HPLC-DAD method was developed and validated to simultaneously determine eight B-vitamins (VBs, namely thiamine, riboflavin, niacinamide, calcium pantothenic, pyridoxine, biotin, folic acid and cyanocobalamin) and phenolsulfonphthalein in rat intestinal perfusate. Chromatographic separation was achieved using an Inertsil ODS-3 column (250 × 4.6 mm i.d., 5 μm) at a temperature of 40°C. Gradient elution mode was applied at the flow rate of 1.0 mL/min with the mobile phase of acetonitrile-30 mm K2 HPO4 (pH 5.80). The method was successfully applied to identify the effects of osmotic pressures on the absorption of the VBs. The absorption profiles of single and mixed VBs were also compared. Histological section technology was applied to observe the microstructure of small bowel mucosa after perfusion. The results indicated that each compound possessed a better absorption profile under isotonic conditions than under hypotonic or hypertonic conditions for single or mixed solutions. Compared with single VBs, better absorptions in mixed VBs were observed. Pathological tissue slice test suggested that hypotonic and hypertonic solutions changed or damaged the microstructure of mucosa to varying degrees. Taken together, the investigations indicated that multi-VBs administered orally under isotonic condition could generate fast and complete absorption profiles for VBs.

Tang-luo-ning (TLN) is a traditional Chinese herbal recipe for treating diabetic peripheral neuropathy (DPN). In this study, we investigated mitochondrial protein profiles in a diabetic rat model and explored the potential protective effect of TLN. Diabetic rats were established by injection of streptozocin (STZ) and divided into model, alpha lipoic acid (ALA), and TLN groups. Mitochondrial proteins were isolated from dorsal root ganglia and proteomic analysis was used to quantify the differentially expressed proteins. Tang-luo-ning mitigated STZ-induced diabetic symptoms and blood glucose level, including response time to cold or hot stimulation and nerve conductive velocity. As compared to the normal, there were 388 differentially expressed proteins in the TLN group, 445 in ALA group, and 451 in model group. As compared to the model group, there were 275 differential proteins in TLN group and 251 in ALA group. As compared to model group, mitochondrial complex III was significantly decreased, while glutathione peroxidase and peroxidase were increased in TLN group. When compared with ALA group, the mitochondrial complex III was increased, and mitochondrial complex IV was decreased in TLN group. Together, TLN should have a strong antioxidative activity, which appears to be modulated through regulation of respiratory complexes and antioxidases.

目的 观察糖络宁对糖尿病大鼠背根神经节线粒体DNA、8-羟基脱氧鸟苷(8-OHdG)及线粒体结构的影响.方法 选取14只SD大鼠作为正常组,其余SD大鼠采用链脲佐菌素制作糖尿病大鼠模型,造模成功后,将其随机分为模型组、西药组(α-硫辛酸)、中药组(糖络宁),共给药8周,给药结束后,检测线粒体DNA水平、8-OHdG水平,并运用电镜观察线粒体内部结构.结果 与正常组比较,模型组大鼠神经细胞线粒体DNA、8-OHdG水平明显增加(P＜0.01);与模型组比较,中药组与西药组神经细胞线粒体DNA、8-OHdG水平明显降低(P＜0.01).与正常组比较,模型组大鼠DRG线粒体肿胀明显,内部结构破坏严重,线粒体内特异结构嵴消失;而中药组大鼠DRG线粒体结构相对完整,线粒体嵴保存完好;西药组大鼠DRG线粒体也存在轻度肿胀,内部结构不完整,嵴显示不清楚.结论 糖尿病大鼠神经细胞中线粒体会发生明显改变,其内部结构严重破坏,DNA表达过度升高,DNA的氧化损伤也非常明显.糖络宁可明显减低线粒体DNA表达,减少氧化损伤,缓解线粒体结构的破坏,这是糖络宁治疗糖尿病周围神经病变的机制之一.

目的:观察糖脂平对胰岛素抵抗大鼠骨骼肌IRS-1磷酸化及GLUT4分布的影响.方法:将24只清洁级SD大鼠随机分为对照组、模型组、中药组和西药组,采用高糖高脂饲料喂养方法造模成功后,分别给予生理盐水、糖脂平和二甲双胍灌胃,给药8周后,用Western Blot方法检测大鼠骨骼肌酪氨酸磷酸化IRS-1和磷酸化Akt的含量,用免疫荧光法观察大鼠骨骼肌GLUT4的分布情况.结果:实验末,与对照组比较,模型组大鼠骨骼肌酪氨酸磷酸化IRS-1和磷酸化Akt含量明显降低,中药组和西药组大鼠的骨骼肌酪氨酸磷酸化IRS-1和磷酸化Akt含量与模型组比较均明显升高,差异有统计学意义(P＜0.01),中药组和西药组的组间差异无统计学意义(P＞0.05).对照组GLUT4分布于骨骼肌肌膜表面,模型组GLUT4膜分布明显减少,出现胞质分布,中药组和西药组GLUT4的膜分布较模型组明显改善.结论:糖脂平通过促进I RS-1的酪氨酸磷酸化,激活其下游PI3K,增加磷酸化Akt含量,进而使胞质内GLUT4膜转位增加,从而改善胰岛素抵抗.

Objective To observe the effect of Tangzhiping on insulin sensitivity, high sensitive C reactive protein ( hs-CRP ) and tumor necrosis factor-α( TNF-α) in patients with metabolic syndrome ( MS) .Methods 70 MS patients who met with defined criteria were randomly divided into treatment group (n=35) and control group (n=35).Besides the original treatment,Tangzhiping and rosiglitazone were given to the treatment group and control group separately for 12 weeks.Insulin action index ( IAI) , insulin resistance index ( IRI ) , hs-CRP and TNF-αwere observed before and after treatment in two groups.Results There were 65 patients fulfilled this trial, among which 33 were treated with Tangzhiping, and 32 were treated with rosiglitazone.IAI were all increased significantly in two groups than those before treatment(P <0.01).There was no statistical significance between two groups(P>0.05).IR were all decreased in both groups than those before treatment ( P<0.01).There was no statistical significance between two groups(P>0.05).The levels of hs-CRP were all higher than the reference value in two groups before treatment.The level of hs-CRP were all decreased in two groups than those before treatment ( P<0 .01 ) , but there was no statistical significance between two groups ( P>0.05).The level of TNF-αwere all decreased in two groups than those before treatment (P<0.01), but there was no statistical significance between two groups( P >0.05).Conclusions Tangzhiping could improve insulin sensitivity of patient with MS.It could also decrease the levels of hs-CRP and TNF-α.

Objective To observe the effect of Chinese herbal compound Tangluoning on 3 kinds of antioxidants mi-tochondrial dorsal root ganglion cells in diabetic rats. Methods There were 40 SD male rats, 7 of them were randomly select-ed as the control group, the rest 33 were used to establish the streptozotocin ( STZ) diabetic rat model, 29 rats of the model were randomly divided into model group with 9 rats, treatment group with 10 rats, Chinese medicine group with 10 rats, they were given saline, alpha lipoic acid and Tangluoning respectively, they was given the medicine for 8 weeks, mitochondria of rat manganese superoxide dismutase ( MnSOD) , glutathione peroxidase ( GPX) , catalase ( CAT) activity changes of the dor-sal root ganglion cells were observed. Results Compared with the control group, the model group rats’ mitochondrial Mn-SOD, GPX, the activity of CAT (U/mg protein) decreased significantly (32. 16 ± 4. 75 vs. 20. 17 ± 3. 31, 45. 67 ± 5. 64 vs. 30. 19 ± 4. 33, 2. 87 ± 0. 47 vs. 1. 24 ± 0. 34, P <0. 01);compared with the model group, treatment group and the tradition-al hinese medicine group’ s mitochondrial MnSOD, GPX, the activity of CAT were significantly improved (30. 78 ± 5. 27, 39. 10 ± 7. 67, 2. 56 ± 0. 31, 29. 14 ± 3. 79, 39. 43 ± 6. 23, 2. 49 ± 0. 28, respectively, P <0. 01). Conclusion It proved that the Tangluoning would significantly improve the 3 kinds of antioxidant activity in dorsal root ganglion mitochondria of dia-betic rats, which maybe the mechanism of Tangluoning for prevention and treatment of diabetic peripheral neuropathy.

Objective To observe the curative effect of soothing liver for dredging collaterals formula on diabetes combined with non-alcoholic fatty liver disease ( NAFLD ) .Methods 120 patients suffering diabetes combined with NAFLD were randomly divided into treatment group ( n=60 ) and control group ( n=60) .Based on controlling of blood glucose, health education and changing life style were conducted for the control group, soothing liver for dredging collaterals formula were given to the treatment group. Results In treatment group ( n =60 ) , 5 cases got complete remission ( 8.33%) , 31 cases had significant effect ( 51.67%) , 17 cases showed effective ( 28.33%) , 7 cases were presented as ineffective (11.67%), the total effective rate was 88.33%; In control group ( n=59), 2 cases got complete remission (3.39%), 12 cases had significant effect (20.34%), 16 cases showed effective (27.12%), 29 cases were presented as ineffective (49.15%), the total effective rate was 50.85%. Ridit analyze showed U=-5.122, P<0.001, which indicated the treatment group was superior to the control group.Symptoms of Chinese medicine in both groups decreased significantly compared that before treatment (P<0.01), and treatment group decreased more than control group (P<0.05), which indi-cated treatment group was superior to control group.ALT,AST,TG,TC and LDL-C of both groups de-creased significantly compared with that before treatment (P<0.05,P<0.01), and ALT, AST, TG, TC, LDL-C of treatment group decreased more than control group (P<0.05).BMI of treatment group was significantly lower than that before treatment (P<0.01), while in control group, BMI showed no significant differences before and after treatment (P>0.05).Conclusions Soothing liver for dredging collaterals formula has good effect on diabetes combined with non-alcoholic fatty liver disease.

目的 探讨糖络宁浸膏治疗糖尿病周围神经病变的可能作用机制.方法 采用一次性腹腔内注射大剂量链脲佐菌素(60 mg/kg)诱导糖尿病大鼠模型.将造模成功大鼠随机分为模型组、中药组、西药组,每组23只,另设健康大鼠15只为正常组.中药组予糖络宁浸膏按生药20g/ (kg·d)灌胃,西药组予α-硫辛酸20 mg/(kg·d)灌胃,正常组和模型组大鼠予等体积蒸馏水灌胃,连续12周.观察各组大鼠血清和坐骨神经中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,大鼠背神经根节(DRG) p38 MAPK、p-p38 MAPK、p46JNK、p-p46JNK、ERK1/2、p-ERK1/2蛋白表达. 结果 与正常组比较,模型组大鼠血清、坐骨神经SOD活性显著降低,而MDA含量均显著增多(P＜0.01);与模型组比较,中药组和西药组大鼠血清、坐骨神经SOD活性均显著增强,MDA含量均显著减少(P＜0.01).各组大鼠DRG的p38 MAPK、p46JNK、ERK1/2总蛋白表达量相近,组间比较差异均无统计学意义(P＞0.05);与正常组比较,模型组大鼠DRG的p-p38 MAPK、p-p46JNK、p-ERK1/2活性蛋白表达均明显增高(P＜0.05),而中药组、西药组大鼠DRG的p-p38 MAPK、p-p46JNK、p-ERK1/2活性蛋白表达均较模型组明显减弱(P＜0.05). 结论 糖络宁浸膏具有显著降低糖尿病大鼠血清、坐骨神经MDA含量,提高血清、坐骨神经SOD活性的作用,有效抑制糖尿病大鼠DRG的p-p38 MAPK、p-p46JNK、p-ERK1/2活性蛋白表达,从而抑制氧化应激反应,对MAPK信号转导通路具有负性调控作用.

Osteocalcin (OC) secreted by osteoblasts is a sensitive and specific indicator of osteoblast activity.Recently,it has been found that osteocalcin serves as an important mediator of endocrine function.Undercarboxylated OC can promote insulin secretion and β-cell proliferation,and lower glucose and lipid levels,suggesting that osteocalcin might play a major role in the regulation of energy metabolism.These findings provide a new insight for the treatment of metabolic diseases such as obesity and diabetes.

Objective: To observe the therapeutic effects and antioxidative effect of Tangluoning(TLN) on diabetic peripheral neuropathy(DPN).Methods: 210 DPN patients who were confirmed to the diagnostic criteria were randomly divided into the treatment group(105 patients) and control group(105 patients).On the basis of routine treatment,the patients in treatment group were given TLN.The patients in control group were given methycobal.The changes of symptoms,nerve conductive velocity and the content of malonaldehyde(MDA),the activity of superoxide dismutase(SOD) were observed in both groups.Results: The total effective rate of treatment group was 89.9%,which was obviously superior to that in control group(71.4%)(P0.05).There were significant differences in the improvement of nerve conductive velocity between two groups(P0.05).After treatment,MDA content decreased significantly and the level of SOD increased significantly in both groups(P0.05),oxidative stress reactions of patients in both two groups were significantly improved and the effect of treatment group was superior to that of control group,the difference was significant(P0.05).There were no obvious side effects during the treatment.Conclusion: TLN could obviously improve therapeutic effect on DPN by protecting against oxidative stress.

To identify a safe and effective Impaired Glucose Tolerance (IGT) intervention program using Traditional Chinese Medicine (TCM) supported by Standard Health Care Advice (SHCA) for the evidence-based TCM intervention in IGT and evidence-based prevention of type 2 diabetes. A total of 510 IGT patients were randomly assigned into either control or TCM intervention group (255 patients for each group). The control group received standard health care according to SHCA. The intervention group also received TCM intervention in addition to standard health care. The study was conducted over a three-year follow-up. At the end of three years follow-up, accumulative incidence and average annual incidence rate of diabetes in the control group was 43.86% and 14.62% respectively. Accumulative incidence and average annual incidence rate of diabetes in the TCM intervention group was 22.17% and 7.39% respectively. Compared with the control treatment, TCM intervention can reduce the relative risk of IGT patients progressing to type 2 diabetes by 49.45% and absolute risk by 21.69%. In the TCM intervention group, oral glucose tolerance test (OGTT), 2 h glucose, glycated hemoglobin, insulin resistance and body mass index were all significantly improved when compared to the control group. No significant side effect was observed during the follow-up in the TCM group. The SHCA-supported TCM intervention can reduce the conversion rate of IGT to diabetes and improve insulin resistance; therefore, it is a safe and effective IGT intervention strategy.

Objective:To investigate the effect of Tangzhiping on serum adiponectin level and the mRNA expression of adiponectin in epididymal fat pads in rats with insulin resistance(IR).Method:Twenty-eight SD rats were randomly divided into control group,model group,Chinese medicine group and Western medicine group.Rat model of IR was induced by high lipid and salt diet.Chinese medicine group was treated with Tangzhiping and Western medicine group was treated with rosiglitazone for 8 weeks.8 weeks later,ELISA was used to detect serum adiponectin level and RT-PCR was used to detect the mRNA expression of adiponectin in epididymal fat pads.Result:The serum adiponectin level and mRNA expression of adiponectin in epididymal fat pads were significantly reduced in model group when compared with control group.The serum adiponectin level of Chinese medicine group was markedly higher than that of model group.Moreover,adiponectin mRNA expression in Chinese medicine group was also up-regulated markedly.Conclusion:The increase of adiponectin mRNA expression in adipose tissue and circulating concentration may play a role in the protective effect of Tangzhiping against insulin resistance and atherosclerosis.

In China, there are more than one hundred million people with diabetes, among which 60% have diabetic peripheral neuropathy (DPN). However, because of the unclear mechanism there is no effective drug for DPN. In this review, we present the current oxidative stress hypothesis and the relationship between the classical and accepted DPN mechanism pathways and oxidative stress. Furthermore, the two signal pathways are important for oxidative stress. Recent studies have focused on the intracellular oxidative stress, especially from mitochondria. As the foremost energy metabolic organelle mitochondria is affected in many aspects after hyperglycemia. Better understanding of the relationship between DPN and oxidative stress may provide insights into new drug therapies. [N A J Med Sci. 2013;6(2):87-90. DOI: 10.7156/najms.2013.0602087]

现代医学的研究表明,骨质疏松症是遗传因素和环境因素共同参与的多因素复杂疾病.环境因素中,营养、运动、饮酒等个人后天生活方式是决定疾病发生与发展的重要因素,因此在骨质疏松症的预防方面,尤宜重视营养与运动等生活方式.这些环境因素在中医看来,它们与中医"脾主运化"及"脾合肌肉主四肢"的生理机能密切相关,与中医对骨质疏松症是以脾虚为本的病机认识趋于一致.本文从现代医学认为的引起骨质疏松的环境因素方面,探讨了脾虚在骨质疏松发生和发展中的关键作用,目的 在于促进对骨质疏松症的中西医认识与沟通,深化中医对骨质疏松症是以脾虚为本的病机认识,为提高中医防治骨质疏松症的防治效果提供参考与帮助.

Diabetic peripheral neuropathy (DPN) is a common microvascular complication of diabetes associated with high disability rate and low quality of life. Tang-Luo-Ning (TLN) is an effective traditional Chinese medicine for the treatment of DPN. To illustrate the underlying neural protection mechanisms of TLN, the effect of TLN on electrophysiology and sciatic nerve morphology was investigated in a model of streptozotocin-induced DPN, as well as the underlying mechanism. Sciatic motor nerve conduction velocity and digital sensory nerve conduction velocity were reduced in DPN and were significantly improved by TLN or α -lipoic acid at 10 and 20 weeks after streptozotocin injection. It was demonstrated that TLN intervention for 20 weeks significantly alleviated pathological injury as well as increased the phosphorylation of ErbB2, Erk, Bad (Ser112), and the mRNA expression of neuregulin 1 (Nrg1), GRB2-associated binding protein 1 (Gab1), and mammalian target of rapamycin (Mtor) in injured sciatic nerve. These novel therapeutic properties of TLN to promote Schwann cell survival may offer a promising alternative medicine for the patients to delay the progression of DPN. The underlying mechanism may be that TLN exerts neural protection effect after sciatic nerve injury through Nrg1/ErbB2→Erk/Bad Schwann cell survival signaling pathway.

Objective To investigate the effect of Tangzhiping on serum TNF-α level and the mRNA expression of TNF-α in epididymal fat pads in rats with insulin resistance(IR).Methods Twenty-eight SD rats were randomly divided into control group,model group,Chinese medicine group and western medicine group.The rat model of IR was established by feeding high-fat and high-salt diet.Rats in Chinese medicine group were treated with Tangzhiping and rats in western medicine group were treated with rosiglitazone for 8 weeks.Eight weeks later,radioimmune assay was used to detect the serum level of TNF-α and RT-PCR was used to detect the mRNA expression of TNF-α in epididymal fat pads.Results Serum TNF-α level of model group was(1.78±0.13)ng/mL,which was significantly higher than that of control group.Treatment with Tangzhiping or rosiglitazone reduced serum TNF-α level to(1.46±0.13)ng/mL and(1.32±0.16)ng/mL(P<0.01),respectively.Compared with control group,TNF-α mRNA expression in rat adipose tissue was significantly higher in model group(P<0.01).After treated with Tangzhiping or rosiglitazone,TNF-α mRNA expression in adipose tissue was decreased by 30.2% and 31.6%(P<0.01),respectively.Conclusion Decreased serum level of TNF-α and downregulated TNF-α mRNA expression by Tangzhiping may contribute to its role in improving IR and protecting against atherosclerosis.

目的 观察糖脂平对喂养型胰岛素抵抗大鼠骨骼肌线粒体超微结构及数量的影响.方法 采用高脂高盐饲料喂养的方法建立胰岛素抵抗大鼠模型18只,随机分为模型组、糖脂平组、二甲双胍组各6只,另有6只正常大鼠作为对照组,连续给药8周.取大鼠腓肠肌常规处理后用透射电镜观察骨骼肌线粒体密度、体积及超微结构改变,用PCR方法检测骨骼肌线粒体数量.结果 胰岛素抵抗模型大鼠骨骼肌线粒体呈轻度肿胀,结构模糊不清,部分出现空泡样变,嵴部分断裂；经中药糖脂平治疗后,骨骼肌线粒体超微病理改变明显减轻,但仍不能恢复正常状态.模型组大鼠骨骼肌线粒体16s rRNA表达量明显减少,提示线粒体数量减少,经糖脂平治疗后,胰岛素抵抗大鼠骨骼肌线粒体的数量明显增加.结论 中药糖脂平可明显改善胰岛素抵抗大鼠的线粒体结构和数量,糖脂平改善胰捣素对抗和调整糖脂代谢紊乱的作用可能与改善骨骼肌线粒体数量和功能有关.