[Metabolomics in Diabetic Neuropathy].

Diabetic neuropathy is a common diabetic complication.The application of metabolomics in the research on diabetic neuropathy is beneficial for us to understand the pathophysiological processes and overall metabolic disturbance of the nervous system under the condition of hyperglycemia,decipher the pathogenesis of diabetic neuropathy,and mine the potential biomarkers for clinical diagnosis and treatment.Long-term hyperglycemia may lead to disorders in multiple pathways,such as tricarboxylic acid circle,amino acid metabolism,and lipid metabolism.These metabolic changes are closely associated with the injuries of the peripheral and central nervous system.In the paper,we reviewed the metabolomics-based studies about diabetic neuropathy in the last five years.

[Advances in Noninvasive Methods for Screening and Evaluating Diabetic Peripheral Neuropathy].

Diabetic peripheral neuropathy(DPN),a chronic diabetic microvascular complication with a high incidence among diabetic patients,increases the risk of diabetic foot and amputation.Many methods are available for screening and evaluating DPN,including traditional 10 g monofilament,tuning fork and vibration perception,and tendon reflex tests,which should be combined with some nerve function score systems to improve the detection rate and accuracy for DPN.In recent years,a number of noninvasive new techniques have been developed for the evaluation of nerve injury,such as corneal confocal microscopy,quantitative sensory testing,current perception threshold test,sympathetic sudomotor function evaluation,and quantitative detection of skin advanced glycation end products.This paper reviews these noninvasive methods for screening and evaluating DPN to help clinicians detect and focus on DPN early.

Humanistic Spirit Contained in Traditional Chinese Medicine should Be Valued.

Medicine is a science studying human's health and diseases as well as the regularity between them. Its research subject is human, who possess natural attribute, psychological attribute and social attribute. Therefore, medicine is bound to possess humanistic attribute. Rooted in Chinese traditional culture, Traditional Chinese Medicine contains abundant humanistic thoughts, for instance, pursuing the unity of human and nature, advocating the vital importance of life, sticking to the virtue of "medicine being humane art", abiding by the principle of "Benevolence prior to interest", complying with the medical rule of "Respecting peers". These are the very concrete reflections of medical humanistic spirit. In this article we aim to explore the humanistic thoughts contained in Traditional Chinese Medicine, and try to inherit and carry forward the spirit to better relieve the tensions between doctors and patients and improve the quality of medical services.

[Research Advances in Autophagy and Diabetic Neuropathy].

Recent studies have found that autophagy is involved in the development of many chronic complications of diabetes. However,the specific mechanism between autophagy and diabetic neuropathy(DN)remains unclear. This article reviews the latest research on the pathogenesis of autophagy and DN,with an attempt to find new targets and ideas for the treatment of DN.

Advances in the Relationship between Adipokines and ß-cell Failure in Type 2 Diabetes Mellitus.

ß-cell failure coupled with insulin resistance plays a key role in the development of type 2 diabetes mellitus (T2DM). Changed adipokines in circulating level form a remarkable link between obesity and both ß-cell failure and insulin resistance. Some adipokines have beneficial effects,whereas others have detrimental properties. The overall contribution of adipokines to ß-cell failure mainly depends on the interactions among adipokines. This article reviews the role of individual adipokines such as leptin,adiponectin,and resistin in the function,proliferation,death,and failure of ß-cells. Future studies focusing on the combined effects of adipokines on ß-cells failure may provide new insights in the treatment of T2DM.

Culturing Schwann Cells from Neonatal Rats by Improved Enzyme Digestion Combined with Explants-culture Method.

Objective To develop an improved method for culturing Schwann cells(SCs) by using both enzyme digestion and explants-culture approaches and compared with traditional explants-culture method and general hemi-explants-culture method. Methods Bilaterally sciatic nerves and brachial plexus nerves were dissected from 3 to 5-day-old neonatal SD rats and explants-culture method,general hemi-explants-culture method,and improved enzyme digestion combined with explants-culture method were adopted to culture SCs,respectively. SCs were digested and passaged after 7 days in culture and counted under the microscope. The purity of SCs was identified by S-100 immunofluorescence staining. Results The SCs of improved method group grew fastest and the total number of cells obtained was(1.85±0.13)×10(6);the SCs of the hemi-explants-culture method group grew slower than the improved method group and the total number of cells obtained was (1.10±0.10)×10(6);the SCs of the explants-culture method group grew slowest and the total number of cells obtained was (0.77±0.03)×10(6).The total number of cells obtained showed significant difference among the three groups(P<0.01). Immunofluorescence staining showed that the SCs purity was (95.73±1.51)% in the improved method group,(84.66±2.68)% in the hemi-explants-culture method group,and (74.50±4.23)% in the explants-culture method group(P<0.01). Conclusion The improved enzyme digestion combined with explants-culture method can obtain sufficient amount of high-purity SCs in a short time and thus may be applied in further research on peripheral nerve regeneration.

Effects of Chinese Medicinal Compound Jinmaitong on the Expression of Nitrotyrosine andNerve Growth Factor in the Dorsal Root Ganglia of Diabetic Rats.

Objective To study the effects of Chinese medicinal compound Jinmaitong(JMT) on the expressions of nitrotyrosine (NT) and nerve growth factor (NGF) in dorsal root ganglia of diabetic rats. Methods Experimental rat diabetic models were established by the intraperitoneal injection of streptozotocin. Rat models were then randomly divided into four groups including normal control group (Con group),diabetes mellitus group (DM group),Jinmaitong group(JMT group)(treated with JMT similar to the fifteen-fold dose of adult recommended dosage),and taurine group(Tau group)(treated with Taurine similar to the fifteen-fold dose of adult recommended dosage),with 10 rats in each group. The Con and DM groups were treated with distilled water at a daily dose of 1 ml/100 g. All rats were given intragastric administration for 16 weeks and then killed. Body weight and blood glucose were detected before and at the 4th,8th,12th,and 16th week after treatment. The pain threshold to mechanical stimulation with von Frey filament were carried out before death. The expressions of NT and NGF in dorsal root ganglion were detected by immunohistochemistry and Western blot analysis,respectively. Results Immunohistochemistry showed that the average optical density (AOD) of NT expression in DM group were significantly higher than those in control group (P=0.000),and the AOD of NGF was significantly lower than the control group (P=0.006).The AOD of NT(P=0.000,P=0.000) in both treatment groups decreased significantly and the AOD of NGF(P=0.000, P=0.004)significantly increased compared with DM group. The AOD of NT in JMT group was significantly lower than Tau group (P=0.004). Western blot analysis showed that the protein level of NT in DM group was significantly higher than that in control group (P=0.000),and the protein level of NGF was significantly lower than that in control group (P=0.000). Compared with the DM group,the protein level of NT in both treatment groups significantly decreased (P=0.001,P=0.000),and the protein level of NGF increased significantly (P=0.000,P=0.001). Conclusion Traditional Chinese medicine JMT can obviously up-regulate the expressions of NGF and reduce the NT levels in dorsal root ganglia of diabetic rats.

[Progress in study of antioxidant effects of Coptis chinensis and its major contributions to diabetes treatment/therapy].

Coptis chinensis, a traditional Chinese medicine, has been found to have multiple pharmacological effects recently. Some research showed that C. chinensis has antioxidant effects, including scavenging oxygen free radicals, alleviating lipid peroxidation, enhancing activity of antioxidant enzymes, et al. C. chinensis may inhibit several classical pathological pathways in diabetes. C. chinensis is a potential medicine to prevent and treat diabetes mellitus and its complications. This review focuses on the recent research progress in the study of antioxidant effects of C. chinensis and its major contributions to diabetes treatment/therapy.

Quercetin protects rat dorsal root ganglion neurons against high glucose-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition.

AIM: To examine the effects of quercetin, a natural antioxidant, on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons of rats. METHODS: DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of NF-кB, IкBα, phosphorylated IкBα and Nrf2 was examined using RT PCR and Western blot assay. The expression of hemeoxygenase-1 (HO-1), IL-6, TNF-α, iNOS, COX-2, and caspase-3 were also examined. RESULTS: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway. Co-treatment with quercetin (2.5, 5, and 10 mmol/L) dose-dependently decreased HG-induced caspase-3 activation and apoptosis. Quercetin could directly scavenge ROS and significantly increased the expression of Nrf-2 and HO-1 in DRG neurons. Quercetin also dose-dependently inhibited the NF-κB signaling pathway and suppressed the expression of iNOS, COX-2, and proinflammatory cytokines IL-6 and TNF-α. CONCLUSION: Quercetin protects rat DRG neurons against HG-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition, thus may be beneficial for the treatment of diabetic neuropathy.

[Effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion in diabetic rats].

OBJECTIVE: To study the effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion (DRG) in rats with diabetic peripheral neuropathy. METHODS: Sixty male SD rats were randomly divided into normal group and model groups. The diabetic rat models were established using Streptozotocin (STZ) method (60 mg/kg of intraperitoneal injection), and then randomly divided Jinmaitong low, middle, and high-dose groups and vitamin C group. All the experimental rats were sacrificed at 16-week and then the DRG was isolated. The morphological changes of DRG were observed using the Nissl's staining, and the NADPH oxidase subunit p22-phox, Cyt C, Bcl-2, and Caspase-3 of DRG in rats were detected by immunohistochemistry and quantitative reverse transcription PCR (qRT-PCR). Cell apoptosis was detected by TUNEL. RESULTS: Compared with the model group, the expressions of NADPH oxidase subunit p22-phox protein, Cyt expression of C protein, Caspase-3 protein, and mRNA cell apoptosis rate in each treatment group significantly decreased whereas the expressions of Bcl-2 mRNA and protein significantly increased (P<0.05 or P<0.01). The Jinmaitong high-dose group had the best effect and was significantly different from that of the vitamin C group (P<0.01). CONCLUSIONS: Jinmaitong capsule can prevent the nerve injury in rats with diabetic peripheral neuropathy by inhibiting oxidative stress and decreasing the apoptosis. The high-dose Jinmaitong capsule has the best effect and is superior to vitamin C.

Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION: SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

[Effects of Chinese herbal medicine Jinmaitong-medicated serum on inducible nitric oxide synthase and NADPH oxidase p22-phox subunit of rat Schwann cells cultured in high-glucose medium].

OBJECTIVE: To investigate the effects of medicated serum prepared by administration of Jinmaitong (JMT), a compound Chinese herbal medicine, on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22-phox subunit and inducible nitric oxide synthase (iNOS) of rat Schwann cells cultured in high-glucose medium. METHODS: Wistar rats were divided into normal control group (distilled water), JMT (JMT at dose of 1.31 g/(kg·d)) group and vitamin C (vitamin C at dose of 0.08 g/(kg·d)) group to prepare medicated serum. Bilateral sciatic nerves of new born Wistar rats were used to separate Schwann cells. Schwann cells cultured in high-glucose medium were divided into high glucose group (cultured with 50 mmol/L glucose medium), JMT group (cultured with JMT-medicated serum) and vitamin C (VC) group (cultured with VC-medicated serum). Schwann cells cultured in DMEM were used as the normal control. After 48 h culturing, the expression of iNOS was detected by immunofluorescence method and p22-phox mRNA was tested by real-time fluorescent quantitative polymerase chain reaction. RESULTS: The expression levels of iNOS and p22-phox mRNA in the high glucose group were higher than those in the normal control group (P<0.01). Compared with the high glucose group, expressions of iNOS protein and p22-phox mRNA in JMT group were significantly decreased (P<0.01) and JMT-medicated serum had better effect than VC (P<0.01). CONCLUSION: JMT-medicated serum can down-regulate the expressions of iNOS protein and NADPH oxidase p22-phox subunit mRNA of Schwann cells cultured in high-glucose medium.

Jinmaitong ameliorates diabetes-induced peripheral neuropathy in rats through Wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinmaitong (JMT) is a prescription of Traditional Chinese Medicine, which is composed of ten herbal drugs and two animal drugs. It has long been used for the treatment of diabetic peripheral neuropathy (DPN). AIM OF STUDY: Wnt/ß-catenin pathway is considered as an essential and direct driver of myelinogenesis. This study aims to evaluate the protective effect of JMT against DPN dynamically during a 16-weeks' treatment, and to investigate the underlying mechanism in which the Wnt/ß-catenin pathway is involved. MATERIALS AND METHODS: Diabetic model was induced by single intraperitoneal injection of Streptozotocin (STZ) using male Sprague-Dawley rats. The model rats were divided into five groups and administrated with JMT at three doses (0.437, 0.875, and 1.75 g/kg per day), neurotropin (positive drug, 2.67 NU/kg per day), and placebo (deionized water), respectively, for continuous 8 weeks (n = 9-10), 12 weeks (n = 8-10), or 16 weeks (n = 7-9). Meanwhile, rats in control group were administrated with placebo (n = 10 for 8 weeks, n = 9 for 12 and 16 weeks, respectively). Blood glucose and body weight were monitored every four weeks. Mechanical allodynia was assessed using mechanical withdrawal threshold (MWT) test. The morphological change of sciatic nerves were observed by transmission electron microscope (TEM) and hematoxylin and eosin (HE) stain. The mRNA and protein levels of targeted genes were evaluated by quantitative real time-PCR and western bolt, respectively. Myelin protein zero (MPZ) and mediators involved in Wnt/ß-catenin pathway, such as ß-catenin, glycogen synthase kinase 3ß (GSK-3ß), and WNT inhibitory factor-1 (WIF-1), were compared among different groups after treatment of 8, 12, and 16 weeks, respectively. RESULTS: The mechanical allodynia and peripheral nerve morphology were degenerated in DPN rats over time, and notably improved after JMT-treatment of 12 and 16 weeks. The decreased MPZ level in DPN rats were also significantly amended by JMT. More importantly, we found that the suppressed Wnt/ß-catenin pathway in sciatic nerves of DPN rats was overtly up-regulated by JMT in a time-dependent manner. Among the three doses, JMT at the middle dose showed the best effect. CONCLUSIONS: JMT effectively ameliorated diabetic-induced peripheral neuropathy, which was mediated by the activation of Wnt/ß-catenin signaling pathway. This study provided new perspective to understand the neuroprotective mechanism of JMT.

Effects of Hirudin on High Glucose-Induced Oxidative Stress and Inflammatory Pathway in Rat Dorsal Root Ganglion Neurons.

OBJECTIVE: To investigate protective effects of hirudin on oxidative stress and apoptosis of spinal dorsal root ganglion cells in high-glucose rats at the cellular and molecular level. METHODS: Dorsal root ganglion neurons (DRGn) were harvested from embryonic day in 15 SD rats, purified and identificated after primary culture. They were divided into the normal control group, high-glucose (HG) group, positive control (alpha-lipoic acid, ALA) group, low-dose hirudin group (H1), medium-dose hirudin group (H2) and high-dose hirudin group (H3). The control group was cultured by neuron specific culture medium, while the HG group was cultured by neuron specific culture medium and 20 mmol/L glucose (HG medium). The hirudin groups were cultured by HG medium+0.25 IU/mL hirudin (H1), HG medium+0.5 IU/mL hirudin (H2) and HG medium+1 IU/mL hirudin (H3). The ALA group was cultured by HG medium+100 µ mol/L ALA. 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenylt etrazolium bromide (MTT) assay was used to explore the optimum concentration and intervention time. Flow cytometry assay was used to detect the level of reactive oxygen series (ROS). Western blot and quantificational realtime polymerase chain reaction (qRT-PCR) were used to detect the expression of protein and mRNA of nuclear factor erythroid 2-related factor 2 (Nrf-2), hemeoxygence-1 (HO-1), nuclear factor-κ B (NF-κ B) and Caspase-3. TUNEL assay was used to test the apoptosis rate of different groups. RESULTS: After 24 h of culture, the cell activity of hirudin and ALA groups were higher than that of HG group, and there was a statistical difference between the H1 group and HG group (P<0.05). In hirudin groups, the apoptosis rate of cells, the expression of activated Caspase-3 protein and Caspase-3 mRNA were lower than those of HG group (P<0.01), higher than those of ALA group (P<0.01 or P<0.05). The ROS level of hirudin groups was higher than that of ALA group (P<0.01), lower than that of HG group (P<0.01 or P<0.05). The expression of NF-κ B (P65) protein in H3 group were lower than those of HG group (P<0.05). The expression of Nrf-2 protein in hirudin groups was higher than that of HG group (P<0.01), lower than that of ALA group (P<0.01 or P<0.05). The expression of HO-1 protein in hirudin groups was lower than that of ALA group (P<0.01 or P<0.05), higher than that of HG group (P<0.01 or P<0.05). CONCLUSIONS: The activity of DRGn cells can be promoted by hirudin under HG conditions. The effects of hirudin on the inhibition of HG on DRGn cells damage mainly include scavenging ROS, up-regulating Nrf-2/HO-1 pathway, inhibiting activation of NF-κ B pathway, down-regulating the expression of and Caspase-3 and reducing DRGn cell apoptosis.

Combination of Quercetin, Hirudin and Cinnamaldehyde Promotes Schwann Cell Differentiation and Myelination against High Glucose by Inhibiting ERK Signaling Pathway.

OBJECTIVE: To investigate the therapeutic and synergistic effects of QHC (combination of quercetin (Q), hirudin (H) and cinnamaldehyd (C)) on Schwann cell differentiation and myelination against high glucose (HG) induced injury. METHODS: Primary-culture Schwann cells exposed to HG (50 mmol/L) for 72 h and Schwann cell-dorsal root ganglion (DRG) neuron cocultures exposed to HG (50 mmol/L) for 7 days were employed as in vitro model of diabetic neuropathy. The cells were randomly divided into 10 groups: control (CON, 25 mmol/L glucose), HG (50 mmol/L glucose), HG plus 10 µmol/L quercetin (Q), HG plus 0.04 IU/mL hirudin (H), HG plus 100 nmol/L cinnamaldehyd (C), HG plus 10 µmol/L quercetin and 0.04 IU/mL hirudin (QH), HG plus 10 µmol/L quercetin and 50 nmol/L cinnamaldehyd (QC), HG plus 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (HC), HG plus 10 µmol/L quercetin, 0.04 IU/mL hirudin and 50 nmol/L cinnamaldehyd (QHC) or 10 µmol/L U0126. Cell differentiation was evaluated by periaxin immunofluorescence staining. The protein expression levels of myelin protein zero (P0), myelin basic protein (MBP), myelin-associated glycoprotein (MAG), extracellular signal-regulated kinase (ERK), p-ERK, p-c-Jun, c-Jun, notch intracellular domain (NICD) and the mRNA expression levels of P0, MBP, MAG, Krox-20, Notch1 and Jagged1 were detected by Western blotting and real-time quantitative PCR analysis. The secretion of ciliary neurotrophic factor (CNTF) was determined by enzyme-linked immunosorbent assay (ELISA). The number and length of the myelin segments were evaluated by MBP immunofluorescence staining. The expression and the location of p-ERK in cocultures were detected by MAG and p-ERK immunofluorescence double staining. RESULTS: Co-treatment with Q, C, H and their combination promoted Schwann cell differentiation, increased CNTF secretion, up-regulated the protein and mRNA expressions of myelin, and increased the number and length of the myelin segments (P<0.01 or P<0.05). In particular, the combination therapy of Q, H and C was superior to the respective monotherapy (P<0.01). Combination therapy of QHC exhibited higher inhibitory activities for ERK signaling related molecules than each monomer or the combination of the two monomers (P<0.01). CONCLUSION: QHC combination yielded synergy in promoting Schwann cell differentiation and myelination and the protective effect may involve in the inhibition of ERK signaling pathway, providing scientific evidence for better understanding of combination of Q, H and C in clinical applications.

[Analysis of Chinese medicine syndrome pattern in patients with type 2 diabetes mellitus and its relationship with diabetic chronic complications].

OBJECTIVE: To analyze the Chinese medicine (CM) syndrome pattern of patients with type 2 diabetes mellitus (DM2) and the relationship of CM patterns with the different blood glucose levels controlled and the incidences of diabetic chronic complications. METHODS: CM syndromes in 557 DM2 patients were sorted into 7 patterns, A: the Fei-Wei yin-deficiency with exuberant heat pattern; B: the Pi-qi deficiency pattern; C: the Shen-qi deficiency pattern; D: the Pi-Shen qi-deficiency pattern; E: the Gan-Shen yin-deficiency pattern; F: the both qi-yin deficiency pattern; and G: the both yin-yang deficiency pattern, the concurrent or accompanied excessive syndromes were not taken as the indication for sorting. The blood glucose level, duration of illness and incidence of diabetic chronic complications in patients of different patterns were compared. RESULTS: The CM syndrome patterns commonly encountered in mostly of the 557 patients was pattern F (in 264 patients, accounting for 47.4%); the next was pattern C (95 patients, 17.1%) and E (92 patients, 16.5%). The concurrent syndromes appeared in most patients was blood stasis (501 patients, 89.9%), Gan-qi stagnation was the second (225 patients, 40.4%), and the portion of damp-heat syndrome was also rather large (180 patients, 32.3%). The duration of diabetes mellitus for patients with various patterns was significantly different (P < 0.01), the longest appeared in patients of pattern G, followed by pattern D, C, F, and E in sequence, and patients of pattern A and B had a rather shorter duration. Level of fasting blood glucose was rather higher in patients of pattern A, C, D, F, and G than in those of pattern B and E. Level of glycosylated hemoglobin in patients of pattern G was the highest and in pattern A the second, while in pattern B and E was rather lower. Incidences of diabetic chronic complications, including diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, cerebral infarction, and atherosclerosis in patients of pattern A and B were lower than in those of other 5 patterns (P < 0.05); but the highest incidence of multiple chronic complications revealed in pattern D and G, and that of coronary heart disease revealed in pattern C and G, all showed significant different as compared with other patterns (P < 0.01). CONCLUSION: The most commonly encountered CM syndrome patterns in DM2 patients of early stage are pattern A and B; and those of middle stage are pattern C, D, E and F, various diabetic chronic complications may reveal in this stage; pattern G could be found in patients accompanied with multiple chronic complications and with uncontrolled blood glucose for a long time.

Effects of Mitochondrial Dysfunction via AMPK/PGC-1 α 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 1 α (PGC-1 α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1 α 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-1 α pathway and improving mitochondrial function.

Effects of oral administration of Stephania tetrandra S. Moore on neovascularization of retinal and choroidal capillaries of diabetes in rats.

In rats, an injection of streptozotocin (STZ) elevated blood levels of glucose 4 weeks later (STZ-induced diabetes) and an over-production of microvessels of retinal and choroidal capillaries of eyes developed. A previous study has shown that administration of Stephania tetrandra S. Moore (STSM) in culture prevented the over-production of microvessels of those capillaries of STZ-induced diabetes in vitro. Therefore, the study investigated whether or not orally administered STSM could inhibit over-production of microvessels of those capillaries of STZ injected rats in vivo. When STSM was given at the same time as the STZ injection and continued daily for 7 weeks, STSM prevented the elevation of blood glucose level and over-production of microvessels of those capillaries. When STSM was given after elevation of blood glucose level of glucose (4 weeks after STZ injection) and continued daily for 4 weeks, STSM lowered the elevated blood glucose level but had no effect on the over-production of microvessels of those capillaries. It was inferred that deposition of N(epsilon)(carboxymethyl) lysine in retinal and choroidal tissues, which is induced by STZ-induced diabetes may deteriorate the blood-retinal barrier and the blood-choroidal barrier. One might, therefore, speculate that advanced STZ-induced diabetes may deteriorate the blood-retinal barrier and blood-choroidal barrier. Therefore, STSM may not reach the retinal and choroidal tissues in the posterior ocular region in vivo.

Effect of Jinmaitong serum on the proliferation of rat Schwann cells cultured in high glucose medium.

OBJECTIVE: To investigate the effect of Jinmaitong (JMT) serum on the proliferation of rat Schwann cells (SCs) primarily cultured in high glucose medium. METHOD: SCs 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+or-0.019, 50 mmol/L Glu 0.367+or-0.035, JMT1:2 0.426+or-0.024, Ntp 0.422+or-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.