针刺联合地奥司明治疗内痔湿热下注证的效果研究

目的探讨针刺联合地奥司明治疗内痔湿热下注证患者的疗效。方法选择该院2017年2月至2019年1月收治的84例内痔湿热下注证患者作为研究对象,按照随机数字表法将患者分为两组,每组42例。A组采用针刺联合地奥司明进行治疗,B组采取常规治疗,观察两组疗效、临床症状积分、生活质量(QOL)评分及不良反应发生情况,对比两组治疗结果。结果A组总有效率为92.86%,显著高于B组的80.95%,差异有统计学意义(P<0.05)。治疗前两组便血、肛门坠痛、脱垂及大小便异常等临床症状积分差异无统计学意义(P>0.05),治疗后A组各项评分均低于B组(P<0.05)。治疗前两组的各项QOL评分差异无统计学意义(P>0.05),治疗后A组各项评分均高于B组(P<0.05)。A组不良反应发生率为7.14%,与B组的11.90%比较,差异无统计学意义(P>0.05)。结论针刺联合地奥司明治疗内痔湿热下注证效果显著,可快速缓解相关症状,提高生活质量,不良反应较少,安全性高,值得临床推广使用。     

Protective effect of Diosmin against benzo(a)pyrene‐induced lung injury in Swiss Albino Mice

Diosmin, a naturally occurring flavonoid commonly present in citrus fruit, is known to exhibit anti‐inflammatory, antimutagenic, antioxidant, and free radical scavenging as well as blood lipid lowering activities among others. Diosmin has also been used for the treatment of various diseases including diabetes mellitus and Alzheimer's disease. Our study explores the role of Diosmin in pulmonary toxicity (lung injury) induced by environmental contaminant benzo(a)pyrene [B(a)P]. Swiss Albino Mice (SAM) were administered with either Diosmin 100 or 200 mg/kg body weight daily for 14 days and then challenged with a single dose of B(a)P. On the 15th day, animals were sacrificed; lung tissues and blood were collected for molecular analysis. B(a)P administration in mice induced the thickening of lung epithelium, damaged alveolar architecture, and promoted inflammatory cell infiltration in the lung tissues. Also, B[a]P significantly increased the expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins and decreased antioxidant enzyme levels. Diosmin‐100 and Diosmin‐200 significantly attenuated the damage to lung epithelium, alveolar architecture, and reduced inflammatory cell infiltration in the lung tissues of mice. Diosmin significantly (P < .05) attenuated the levels of oxidative stress markers: lactate dehydrogenase and xanthine oxidase. A decrease in expression of NF‐kB, COX‐2, IL‐6, Bax, cleaved caspase 3, and cleaved PARP proteins in mice was challenged with B[a]P. Diosmin thus could be a promising therapeutic adjuvant against B[a]P‐induced oxidative stress and lung damage.     

地奥司明片的生物等效性

目的研究地奥司明片的人体生物等效性。方法20名健康男性受试者采用2种制剂双周期交叉试验设计,分别单剂量口服1g地奥司明片试验制剂(T)和参比制剂(R)。采用HPLC紫外检测法测定血浆中地奥司明代谢物地奥亭浓度。结果T与R的主要药动学参数分别为:t_(max)(1.04±0.17)和(0.96±0.09)h;ρ_(max)(1150.995±176.231)和(1179.677±203.309)μg·L~(-1);AUC_(0→48)(8206.344±1845.794)和(8589.119±1517.918)μg·h·L~(-1);AUC_(0→∞)(10941.115±3191.603)和(11036.951±2 464.906)μg·h·L~(-1),t(1/2)(21.925±13.042)和(21.360±10.555)h。相对生物利用度:(97.05±21.748)%。药动学参数经多因素方差分析显示周期间与制剂间差异均无统计学意义(P>0.05),双单侧t检验表明接受T与R生物等效的假设,经计算90%置信区间均在规定值内。结论T与R具生物等效性。     

Protective effect of diosmin against diabetic neuropathy in experimental rats

OBJECTIVE:The present study was undertaken to evaluate the effect of diosmin in diabetic neuropathy in type 2 diabetic rats.METHODS:Type 2 diabetes was induced in male Sprague-Dawley rats by single intraperitoneal injection of streptozotocin(35 mg/kg) and high-fat diet.Four weeks after the confirmation of diabetes,diabetic rats were treated with diosmin(50 and 100 mg/kg,p.o.) for next 4 weeks.Rats were evaluated for biochemical,behavioral and oxidative stress parameters.Eddy's hot plate and tail immersion test were performed on 6th,7th,8th,9th and 10th weeks of experiment to assess thermal hyperalgesia and cold allodynia respectively.Further,the walking function test was performed for assessing the motor responses at the end of the treatment schedule.RESULTS:Rats were fed with high-fat diet throughout the experiment schedule and administration of low-dose streptozotocin induced significant elevation in blood glucose level and insulin resistance which was confirmed by oral glucose tolerance test.Treatment with diosmin at doses of 50 and 100 mg/kg significantly restored the reduced body weight,elevated blood sugar and lipid profiles.Further the dose-dependent improvement was observed in thermal hyperalgesia,cold allodynia and walking function in diabetic rats treated with diosmin.Elevated levels of malondialdehyde,and nitric oxide and decreased glutathione levels and superoxide dismutase activity in diabetic rats were restored significantly after the 4 weeks of diosmin treatment.CONCLUSION:Diosmin has shown beneficial effect in preventing the progression of early diabetic neuropathy in rats.     

地奥司明对肾缺血/再灌注大鼠氧化应激及肾功能的影响

目的观察地奥司明(diosmin,DOSM)对大鼠肾缺血/再灌注(ischemia/resperfusion,I/R)肾组织中氧化应激水平及肾功能的影响。方法 180只SD大鼠随机分为3组:假手术组(sham operation,SO)、I/R模型组和DOSM+I/R组。采用ELISA方法测定肾组织中丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)含量的变化,同时检测血肌酐(creatinine,Cr)和尿素氮(blood urea nitrogen,BUN)水平。结果在缺血再灌注后1h、3h、6h和12h肾组织中MDA含量逐渐升高,12h达到高峰,I/R组和DOSM组均显著高于SO组(P<0.01);此后MDA逐渐下降,DOSM组血清MDA水平显著低于I/R组(P<0.01)。随再灌注时间的延长,肾组织匀浆中SOD活性显著降低,并于24h达最低水平,此后开始回升。DOSM组在6h、12h、24h和48h与I/R组相比不同程度地提高SOD的活力(P<0.01或P<0.05),与SO组相比无统计学差异。血Cr和BUN水平在DOSM+I/R组显著低于I/R组(P<0.05或P<0.01)。结论大鼠肾I/R可以引起肾组织的脂质过氧化反应增强,DOSM可通过抗氧自由基损伤及减轻脂质过氧化反应而保护肾功能。     

香叶木苷对人肝癌HepG2细胞凋亡及Bcl-2/Bax基因表达的影响

目的 研究香叶木苷对人肝癌HepG2细胞增殖抑制及诱导凋亡的作用,并探讨其相关分子机制。方法 将HepG2细胞分为对照组和香叶木苷组,香叶木苷组分别加入终质量浓度为1、5、25 μg/mL的香叶木苷DMSO溶液,对照组加入等体积的DMSO。药物处理24 h后,台盼蓝染色及Live/Dead染色检测香叶木苷对HepG2细胞活性的影响;CCK-8及EdU染色检测香叶木苷对HepG2细胞增殖的影响;TUNEL染色检测香叶木苷对HepG2细胞凋亡的影响;实时荧光定量PCR（qRTPCR）及Western blotting法检测香叶木苷对Bcl-2、Bax mRNA和蛋白水平的影响。结果 与对照组比较,香叶木苷降低HepG2细胞活力、抑制细胞增殖,5、25 μg/mL组差异显著（P<0.05、0.01、0.001）;促进HepG2细胞凋亡,各浓度组均差异显著（P<0.01、0.001）,且均呈剂量相关性。经5 μg/mL香叶木苷处理后,HepG2细胞中抗凋亡蛋白Bcl-2的mRNA水平显著降低（P<0.001）,而促凋亡蛋白Bax的mRNA水平显著升高（P<0.001）,Bcl-2/Bax蛋白水平显著降低（P<0.001）。结论 香叶木苷抑制HepG2细胞活力和增殖、促进凋亡,作用机制与调控Bcl-2/Bax表达有关。     

Flavonoid treatment reduces glycation and lipid peroxidation in experimental diabetic rats

It has been reported that flavonoids in vitro have the capacity to inhibit aldose reductase. The aim of this study was to evaluate this property in vivo. We chose diosmin, a freely available and inexpensive flavonoid without major side effects. Streptozotocin diabetic rats were treated for a period of 8 months with diosmin, mixed with their food. Sorbitol accumulation was measured in erythrocytes and in eye lenses. In these tissues diosmin did not appear to inhibit aldose reductase. However, diosmin-treated animals maintained a greater body weight than the untreated group. Although the glycaemic values were the same, and the insulinaemias even lower in the diosmin group, glycated haemoglobin was significantly decreased compared with the untreated animals. Skin collagen fluorescence, an index of collagen glycation, was also significantly decreased in the treated animals. Malondialdehyde, a stable end product of lipid peroxidation, was decreased in the treated animals. Diosmin was well tolerated by the animals. In conclusion, diosmin is a safe and inexpensive product. It cannot inhibit aldose reductase activity in vivo but diosmin causes a significant reduction of the glycation of proteins in diabetic animals. Inhibition of lipid peroxidation is also observed but it is not clear whether or not this phenomenon is a direct consequence of the decreased glycation.     

地奥司明及氢氯噻嗪治疗乳腺癌术后淋巴水肿的疗效分析

目的:对比分析地奥司明、氢氯噻嗪单用及联用对乳腺癌术后淋巴水肿的治疗效果。方法:将2018年10月至2020年04月在我院治疗的乳腺癌术后淋巴水肿的患者共104例,随机分为3组,分别使用氢氯噻嗪单药、地奥司明单药及地奥司明联合氢氯噻嗪进行治疗,观察疗效和生活质量改变情况。结果:和氢氯噻嗪组相比,地奥司明组对乳腺癌术后淋巴水肿的有效率及QOL评分显著提高（P＜0.05）;和地奥司明组相比,地奥司明+氢氯噻嗪组对乳腺癌术后淋巴水肿的有效率及QOL评分显著提高（P＜0.05）。结论:地奥司明联合氢氯噻嗪治疗乳腺癌术后淋巴水肿效果显著。     

低分子肝素钙联合地奥司明防治下肢深静脉血栓形成103例

目的观察低分子肝素钙联合地奥司明防治静脉曲张术后下肢深静脉血栓形成的临床疗效。方法选取2009年10月至2011年10月静脉曲张患者206例,分为治疗组和对照组,各103例。所有患者均行大隐静脉高位结扎剥脱术。治疗组术前4h给予脐周皮下注射低分子肝素钙及口服微粒化地奥司明片,且术后维持口服1周;对照组术前4 h给予脐周皮下注射低分子肝素钙。术后两组均给予脐周皮下注射小剂量低分子肝素钙。观察两组术前、术后1周小腿周径,B超检查有无深静脉血栓,血液生化检查及不良反应发生情况。结果术后1周,对照组小腿周径较术前明显增加(t=11.725,P<0.001),也较同期治疗组粗(t=9.601,P<0.001);B超检查发现对照组术后下肢深静脉血栓总发生率显著高于同期治疗组(矫正χ2=8.199,P<0.05)。结论低分子肝素钙联合地奥司明在降低下肢深静脉血栓发生率方面更有优势,疗效确切且不良反应少,可作为临床防治大隐静脉曲张术后深静脉血栓形成的药物治疗方案。     

Antihyperglycaemic action of diosmin,a citrus flavonoid,is induced through endogenous β‐endorphin in type I‐like diabetic rats

Diosmin is one of the flavonoids contained in citrus and has been demonstrated to improve glucose metabolism in diabetic disorders. However, the mechanism(s) of diosmin in glucose regulation remain obscure. Therefore, we investigated the potential mechanism(s) for the antihyperglycaemic action of diosmin in streptozotocin‐induced diabetic rats (STZ‐diabetic rats). Diosmin lowered hyperglycaemia in a dose‐dependent manner in STZ‐diabetic rats. This action was inhibited by naloxone at a dose sufficient to block opioid receptors. Additionally, we determined the changes in plasma β‐endorphin‐like immunoreactivity (BER) using enzyme‐linked immunosorbent assay (ELISA). Diosmin also increased BER dose‐dependently in the same manner. Repeated treatment of STZ‐diabetic rats with diosmin for 1 week resulted in an increase in the expression of the glucose transporter subtype 4 (GLUT 4) in the soleus muscle and a reduction in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. These effects were also inhibited by naloxone at a dose sufficient to block opioid receptors. Bilateral adrenalectomy in STZ‐diabetic rats eliminated the actions of diosmin, including both the reduction in hyperglycemia and the elevation of plasma BER. In conclusion, our results suggest that diosmin may act on the adrenal glands to enhance the secretion of β‐endorphin, which can stimulate the opioid receptors to attenuate hepatic gluconeogenesis and increase glucose uptake in soleus muscle, resulting in reduced hyperglycemia in STZ‐diabetic rats.