目的:探讨番石榴叶提取物对糖尿病db/db小鼠骨骼肌AMPK-PGC-1α-FNDC5信号通路的影响.方法:实验共纳入24只6周龄雄性db/db小鼠及6只同龄雄性C57BL/6J小鼠,适应性喂养两周后,6只C57BL/6J雄性小鼠作为正常组,db/db小鼠检测空腹血糖≥7.0 mmol/l者视为造模成功,并随机分为模型组和番石榴叶提取物高、中、低剂量组,每组各6只.番石榴叶提取物按高剂量14 mg/kg、中剂量7 mg/kg、低剂量3.5 mg/kg每日进行灌胃,正常组小鼠灌服等量蒸馏水,干预4周.每周监测小鼠进食量、体重和空腹血糖.实验结束后,将小鼠空腹脱臼处死,并从眼眶取血,测定血浆胰岛素水平.Western-blot检测AM PK-α、p-AM PK-α、PGC-1α、FNDC5蛋白在骨骼肌中的表达,以及PGC-1α、UCP-1在脂肪组织中的表达.结果:番石榴叶提取物高剂量组小鼠相比模型组小鼠体重、血糖均显著降低,中剂量组小鼠在第2周血糖也出现明显下降,高、中剂量组小鼠的胰岛素水平均降低.检测蛋白表达结果显示,番石榴叶提取物干预的小鼠骨骼肌P-AM PK-α、PGC-1α、FNDC5蛋白和脂肪组织PGC-1α、UCP-1蛋白的表达均明显高于模型组.结论:番石榴叶提取物可通过增强骨骼肌的AM PK-PGC-1α-FNDC5信号通路传导,诱导白色脂肪组织棕色化,以实现降低血糖、减轻体重.

BACKGROUND: The occurrence and development of osteoporosis are shown to be directly related to the inflammatory response induced by immune dysfunction. OBJECTIVE: To summarize the mechanisms of osteoclast differentiation and formation at cellular and molecular levels, as well as the underlying mechanisms of several kinds of medical herbs against osteoporosis, thus paving ways for finding more effective and safe herbs for anti-osteoporosis.METHODS: PubMed database was retrieved using the English keywords of (osteoporosis OR bone loss) AND lipopolysaccharide AND bone resorption", and WanFang database was searched with the Chinese keywords of "osteoarthritis, receptor activator of nuclear factor-κB ligand, lipopolysaccharide,Dendrobium moniliforme,Portulaca oleracea,Ampelopsis sinica,Schizonepeta".The literatures addressing osteoporosis, inflammation and herbal medicine were screened, and those using lipopolysaccharide-induced mouse models were included. Finally, four eligible literatures were enrolled for review. RESULTS AND CONCLUSION:In vivo experiments,CT images and pathological sections of the cancellous bone in the mouse distal femur show that Dendrobium moniliforme,Purslane oleracea,Ampelopsis sinica,and Schizonepeta exert inhibitory effects on lipopolysaccharide-induced osteoporosis.In vitro experiments reveal that these four kinds of herbs fight against osteoporosis by inhibiting osteoclast differentiation and further reducing bone resorption.

The present study aimed at investigating the effects of Puerarin（PR）, a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vivo assay, female mice were ovariectomized（OVX）, and the OVX mice were fed with a diet containing low, middle, and high doses of PR(2, 4, and 8 mg·d-1, respectively) or 17β-estradiol(E2, 0.03 μg·d-1) for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight, compared with the control. The total femoral bone mineral density（BMD） was significantly reduced by OVX, which was reversed by intake of the diet with PR at any dose, especially at the low dose. In the in vitro assay, RAW264.7 cells were used for studying the direct effect of PR on the formation of osteoclasts. PR reduced the formation of tartrate resistant acid phosphatase（TRAP）-positive multi-nucleated cells in the RAW 264.7 cells induced by receptor activator for nuclear factor-κB Ligand（RANKL）. MC3T3-E1 cells were used for studying the effects of PR on the expression of osteoprotegerin（OPG） and RANKL m RNA expression in osteoblasts. The expression of OPG m RNA and RANKL m RNA was detected by RT-PCR on Days of 5, 7, 10, and 12 after PR exposure. PR time-dependently enhanced the expression of OPG m RNA and reduced the expression of RANKL m RNA in MC3T3-E1 cells. In conclusion, our results suggest that PR can effectively prevent bone loss in OVX mice without any hyperplastic effect on the uterus, and the antiosteoporosis activity of PR may be related to its effects on the formation of osteoclasts and the expression of RANKL OPG in osteoblasts.

BACKGROUND:The gut microbiota in our intestine performs numerous useful functions and has a major impact on the host’s health. Recently some studies have revealed that the gut microbiota cannot only control intestinal activity but also affect bone metabolism by regulating the immune system. OBJECTIVE:To review the new research development in the effects of gut microbiota on bone metabolism. METHODS: We retrieved the PubMed database using “gut microbiota, immune system, bone metabolism, osteoporosis” as keywords. A total of 46 articles were included which were related to gut microbiota, immune system and bone metabolism. For the articles in the same field, those published recently or in authorized journals were selected. RESULTS AND CONCLUSION:Gut microbiota-osteoporosis research wil bridge the gaps between bone physiology, gastroenterology, immunology, and microbiology.In vivo experiments in the germ-free mice and human body have found that the gut microbiota has important effects on bone metabolism, and the intervention of antibiotics, probiotics and prebiotics has further confirmed the effects of gut microbiota on bone mass. The gut microbiota has more obvious effects on bone mass in the adolescent and post-menopause periods.

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.

BACKGROUND:Experimental studies have showed that puerarin has an obvious protective effect on osteoporosis in ovariectomized and orchiectomized mice. But the influence of puerarin in the molecular level in the process of osteoblast differentiation is seldom reported. <br> OBJECTIVE:To observe the effect of puerarin on the mRNA expression of alkaline phosphatase, bone sialoprotein, osteopontin and osteocalcin in osteoblasts. <br> METHODS:The MC3T3-E1 cells from mice cultured in vitro were randomly divided into control group, puerarin group (10-6 mol/L puerarin) and estradiol group (10-7 mol/L estradiol) to observe the effects of puerarin on the differentiation of osteoblasts. mRNA expression of alkaline phosphatase, bone sialoprotein, osteopontin and osteocalcin in MC3T3-E1 cells was determined using RT-PCR method. <br> RESULTS AND CONCLUSION:Puerarin and estradiol both could prolong the expression of alkaline phosphatase that reached the peak at 12 days. Puerarin and estradiol strengthened the mRNA expression of bone sialoprotein at 10 and 12 days, reduced expression of osteopontin at 5 and 12 days, and increased expression of osteocalcin at 10 and 12 days. These results reveal that puerarin can induce the differentiation of cultured osteoblasts by influencing osteoblast differentiation-related protein mRNA expressions, which may be one of the important molecular mechanisms of puerarin for prevention of osteoporosis.

Prior studies of osteoporosis has been focused on local regulation of bone mass. Recent studies have pointed out that the nervous system regulates the bone remodeling through the secretion of the neurotransmitter and extensive peripheral nerve synapses and together with endocrine hormone. They have showed that bone metabolism is an overall control of the body. Among them,the sympathetic nervous system plays a key role in regulating bone mass,which act on the β2-adrenergic receptor of the osteoblastic cells. Central nervous system,leptin and serotonin regulate the bone metabolism by inhibiting or exciting peripheral sympathetic nervous. Here we summarized the recent progress of the research.

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.

Kidney-essence deficiency has been generally considered as the main cause of osteoporosis in pathology,and nourishing renal essence has become the general principle of rehabilitation and medicine use.However,spleen and stomach play the fundamental role of health after birth,qi and blood is the source of transportation and transformation of nutrition.The renal essence can only be replenished by the spleen essence.So,spleen deficiency should be an important reason for osteoporosis.Our first interpretation of the term "bone erosion" in Li Dong-yuan's Pi Wei Lun pointed out that this term covers the category of osteoporosis and the underlying cause of "bone erosion" is spleen deficiency.This article discusses the role which spleen deficiency plays in osteoporosis in aspects of TCM basic theory,different TCM syndrome types,medicine use,etc.It points out that spleen deficiency is the main reason for osteoporosis and more attentions should be paid on invigorating and supplementing spleen and stomach in terms of principles and methods of treatment.Invigorating and supplementing spleen and stomach,or nourishing kidney combined with supplementing spleen,may be the more effective method compared with nourishing kidney alone.

目的:观察中药复方糖络宁对糖尿病大鼠血清NGF含量及坐骨神经组织NGF mRNA表达的影响.方法:采用链脲佐茵素(STZ)制作糖尿病大鼠模型,造模成功后随机分为模型组、西药组和糖络宁高、中、低剂量组并分别给药,共给药12周,另设正常对照组,给药结束后,观察各组大鼠血清NCF含量及坐骨神经组织NGF mRNA表达.结果:与正常对照组比较,模型组大鼠血清NGF含量明显下降;与模型组比较,西药组与糖络宁各剂量组大鼠血清中NGF含量明显升高;糖络宁高剂量组血清NGF含量又明显高于西药组.与正常对照组比较,模型组大鼠坐骨神经组织中NGF mRNA表达明显下降;与模型组比较,西药组与糖络宁中、高剂量组大鼠坐骨神经组织中NGF mRNA表达明显升高.结论:糖络宁可提高糖尿病大鼠血清NGF水平,可上调糖尿病大鼠坐骨神经组织NGF mRNA表达,这可能是糖络宁治疗糖尿病周围神经病变的机制.

目的 观察中药复方糖络宁对糖尿病大鼠坐骨神经山梨醇含量的影响.方法 采用链脲佐菌素诱导糖尿病大鼠模型,造模成功后随机分为模型组、西药组、糖络宁高剂量组、糖络宁中剂量组、糖络宁低剂量组给药,共给药12周,给药结束后,观察糖络宁对大鼠坐骨神经山梨醇的影响.结果 与正常组大鼠比较,所有糖尿病组大鼠坐骨神经组织的山梨醇含量均显著增高(P<0.01);与模型组比较,所有糖络宁治疗组及西药组都能够降低糖尿病大鼠坐骨神经组织中山梨醇含量(P<0.05或P<0.01);而中、高剂量糖络宁组降低山梨醇的作用优于西药组(P<0.05).结论 糖络宁可降低糖尿病大鼠坐骨神经组织山梨醇含量,这可能是糖络宁治疗糖尿病周围神经病变的机制.

目的观察降糖保肾合剂对早期糖尿病肾病(DN)的临床疗效。方法将符合诊断标准的DN患者72例随机分为治疗组(36例)和对照组(36例),在基础治疗的同时,治疗组予降糖保肾合剂;对照组予以福辛普利治疗。观察患者的24小时尿微量白蛋白定量(UAE)、内生肌酐清除率及中医症候积分。结果治疗组总有效率为88.89%,对照组总有效率为63.89%,治疗组明显优于对照组(P<0.05)。2组治疗后24小时UAE均明显降低(P<0.01或0.05),治疗后组间比较,治疗组在降低DN患者UAE方面优于对照组(P<0.05);2组治疗前后内生肌酐清除率(Ccr)明显降低(P<0.01或0.05),治疗后组间比较,治疗组能更好地改善DN患者的高滤过状态(P<0.01)。治疗过程中未见明显的不良反应。结论降糖保肾合剂可显著减少早期糖尿病肾病患者24小时UAE,改善患者的高滤过状态,疗效优于福辛普利。

Objective To review the curative effect of wet compressing of Chinese medicinal,with the actions of supplementing qi,activating blood circulation and detoxify,on refractory ulcer of diabetic foot in yellow stage.Method The patients with refractory ulcer of diabetic foot were randomly divided into the treatment group treated with Chinese medicinal and control group treated with traditional ulcer management.The duration of ulcer development from yellow stage to red stage and TCM symptom integrals of diseased foot were observed.Result The most of symptoms and signs were relieved in two groups.In the aspects of diseased foot temperature,secretion and granulation colour,the treatment group had better curative effect than control group.The duration of ulcer development from yellow stage to red stage was shortened in the treatment group.Conclusion The wet compressing of Chinese medicinal,with the actions of supplementing qi,activating blood circulation and detoxify,had better effects of relieving local infection and regeneration,which can treat effectively diabetic foot gangrene.

Objective To observe quantitative ultrasound(QUS) changes in elderly male patients with type 2 diabetes,and investigate the relationship with blood glucose level,HbA_(1c) and urinary albumin excretion(UAE). Methods There were 79 elderly male patients with type 2 diabetes in the study group,43 patients without diabetes in the control group.Patients with diabetes were divided into four subgroup:Group I:HbA_(1c)<7%,Group IA;UAE<30 mg/24 h,Group IB:UAE>30 mg/24 h,Group II:HbA_(1c).>7%,Group IIA:UAE<30 mg/24 h and Group IIB:UAE>30 mg/24 h.Glucose,HbA_(1c),ALP,Cr,UAE,BUA,SOS and STI were measured.Results Compared with control group,BUA,SOS and STI in diabetic group decreased significantly(P<0.01).BUA,SOS and STI in diabetes subgroup of IIB was significandy lower than in subgroup IIA,subgroup IA and group IB(P<0.05).Conclusion The BUA,SOS,STI are lower in diabetic group than in controls group.The BUA,SOS and STI of patients with abnormal blood glucose and microalbuminuria>30 mg/24 h are decreased more significantly than those with normal blood glucose and microalbuminuria<30 mg/24h.

Objective To sum up and study the distribution characteristics and development laws of TCM syndrome in the patients with type 2 diabetes accompanied by metabolic syndrome. Methods The patients accorded with the diagnostic standard of type 2 diabetes accompanied by metabolic syndrome (n=295) were chosen and given the syndrome differentiation according to the criteria of syndrome differentiation established by the Expert Committee of Diabetes Mellitus of China Association of Chinese Medicine. The clinical symptoms,signs and syndrome distribution in different processes of diabetes were analysed and compared statistically. Results Most of patients had the symptoms and signs of obesity, darkness in lips and tongue, heaviness of head and body, slippery and rapid pulse. The most common syndromes were dampness-heat syndrome and blood-stasis syndrome. The patients with the process of diabetes less than 5 years had mostly dampness-heat syndrome, blood-stasis syndrome and syndrome of heat accumulation in stomach and intestines, those with the process of diabetes for 5 to 10 years had the syndromes of pathogen excess and healthy qi deficiency at the same time, and those with the process of diabetes for more than 10 years had the syndrome of healthy qi deficiency mainly. Conclusion The patients with type 2 diabetes accompanied by metabolic syndrome have the syndrome of pathogen excess mainly at early stage, and then will have syndrome of deficiency complicated with excessiveness along with the development of diabetes. The syndrome of pathogen excess includes qi stagnation, blood stasis, dampness turbid and heat accumulation, among which the most common syndromes are dampness turbid and blood stasis.

Objective:To investigate the effect of Tangluoning(TLN) on sciatic nerve tissue conduction velocity and pathology in streptozotocin(STZ) induced diabetic rats.Methods:STZ induced diabetic rats were randomly divided into diabetic model group,Epalrestat group,TLN high dose group,TLN middle dose group and TLN low dose group.The levels of sciatic nerve conduction velocity and pathology of the animals were checked after 12 weeks’ treatment.Results:Compared with normal group,the MNCV of model group decreased signifi cantly in week 2,week 4,week 8,week 12(P0.01).Compared with diabetic model group,the MNCV of Epalrestat group signifi cantly increased in week 4,week 8,week 12(P0.05 or P0.01).Compared with diabetic model group,The MNCV of low,middle and high dose TLN groups had signifi cant amelioration in week4,week 8,week12(P0.05 or P0.01).Only the high dose TLN group had signifi cant difference in week 12 compared with Epalrestat group(P0.05).There was signifi cant injury in aciatic nerve morhpometrics of diabetic rats,which could be alleviated by TNL in different extent.Conclusion:TLN can improve sciatic nerve conduction velocity and nerve pathomorphology change.

目的观察中药内服联合熏洗治疗糖尿病周围神经病变(DPN)的临床疗效。方法选择符合诊断标准的DPN患者98例,随机分为治疗组和对照组,均口服中药,治疗组同时加用中药熏洗治疗。治疗前后分别观察症状积分、神经传导速度和末梢微循环积分。结果治疗组在改善临床症状方面明显优于对照组,且起效时间短,末梢微循环的改善也优于对照组(P<0.05),但在神经传导速度改善方面与对照组比较差异无统计学意义(P>0.05)。结论联合中药熏洗是治疗DPN的有效方法之一。

Objective:To investigate the effect of TangLuoNing(TLN) on adhesion molecules in streptozotocin(STZ) induced diabetic rats.Methods:STZ induced diabetic rats were randomized to diabetic model group,methycobal group,TLN group.The levels of CD54,CD62P of the animals were checked after 12 weeks,treatment.Results:Compare with normal rats group,CD54,CD62P activities in all diabetic groups were signifi cant higher(P0.01).CD54,CD62P activities in TLN group and Methycobal group were lower.But only the activity of TLN group were signifi cantly lower than the diatetic model group(P0.01).The activity of TLN group was also significantly lower than the Methycobal group(P0.05).Conclusion:TLN can reduce the adhesion molecule CD54 and CD62P activity in diabetic rats' sciatic serum which showed that the depression of vessel in? ammation is one of main effect mechanism of TLN.

Objective To investigate the effects of western medicine combining with traditional Chinese medicine on patients with T2DM and function of islet β cell. Methods 60 Type 2 diabetic patients with poor western medicine controlled Blood glucose were randomly divided into 2 groups, the control group and the trial group. 30 patients from the control group continue the original treatment.The trial group added Jinqijiangtangpian on the basis of the original treatment,8-10 tablets each time, threes times a day. Blood glucose ,C peptide ,HbA1C and blood fat were measured after 12 weeks and HOMA-β as well as Homa-IR were calculated by HOMA model. Results After 12 weeks ,FBG ,2 h PBG ,HbA1C and TC and TG were significantly lower than the control group(P<0.01).No difference were found in fasting insulin and C peptide(P>0.05).2 h postprandial insulin and C peptide rose(P<0.01).Homa-β rose by 10±0.6. Homa-IR declined by 0.7±0.5(P<0.01).Conclusions To the patients with deficiency of both vital energy and yin, treatment of the Chinese formulated product Jinqijiangtangpian on the basis of western medicine can improve the islet β-cell function.

目的:观察循经点穴按摩治疗糖尿病性周围神经病变(DPN)的临床疗效。方法:选择符合标准的DPN患者,随机分为治疗组和对照组,在原治疗方法不变的基础上,治疗组配合中医循经点穴治疗。治疗期间监测血糖、血脂、血压,观察治疗前后的临床症状积分和神经传导速度的变化。结果:治疗组临床疗效优于对照组,在改善临床症状方面也明显优于对照组,而且起效时间短,但在神经传导速度改善方面与对照组比较无统计学意义。结论:循经点穴按摩是治疗DPN的有效方法之一,值得进一步研究。