牛磺熊去氧胆酸结构及性质的研究

本文对牛磺熊去氧胆酸(Tauroursodeoxycholic acid,简称TUDCA)结构及性质进行了研究,结果表明:游离TUDCA是易溶于水的酸性化合物,其1%水溶液pH 2～3;差热分析测得其含两分子结晶水,且mp为180.4℃;元素分析结果,其C、H、N平均含量分别为57.75%、8.77%及2.61%;红外光谱表明具有典型的酰胺基、羟基及磺基吸收;~(13)SCNMR表明酰基C_(24)δ为177.4 ppm,羟亚甲基C_及C_7 δ均为71.7 ppm,牛磺酸基团中C_(25)及C_(26)的δ分别为37.6 ppm及50.8 ppm;质谱分析测得其(MWNa) 为522,与计算值521.70完全相同;比旋光度测定结果,其[α]_D~(17.5)= 43.28°,与计算值相一致;薄层层析结果R_f值为0.3.～0.32;磺酸基试验及其水解产物薄层色谱结果确证其分子中含磺酸基及熊去氧胆酸(UDCA)基团;几种胆酸Gregory-Pascoe反应物吸收光谱还表明,TUDCA分子中牛磺酸基团对显色反应产生显著影响。     

HPLC-UV-ELSD联用检测熊香胶囊中牛磺熊去氧胆酸的含量

目的:HPLC-UV-ELSD联用检测熊香胶囊中牛磺熊去氧胆酸的含量;方法:采用Kromasil C18色谱柱(5μm,4.6mm×250mm),以甲醇-水(0.1%甲酸)(60∶40)为流动相;紫外检测波长为210nm;ELSD漂移管温度105℃,雾化气体(空气)流速2.7L·min-1;结果:牛磺熊去氧胆酸在1.44～5.76μg线形关系良好,紫外检测方式回收率为97%(n=5),RSD2.3%,UV检测方式回收率为101%(n=5),RSD1.5%;结论:与HPLC/UV相比,HPLC/ELSD测定熊香胶囊中牛磺熊去氧胆酸成分的含量结果更准确。     

牛磺熊去氧胆酸对急性胰腺炎大鼠内质网应激蛋白的影响

摘要:目的 观察牛磺熊去氧胆酸（TUDCA）对蛙皮素诱导的急性胰腺炎大鼠内质网应激相关蛋白GRP78/BIP、sXBP-1、pJNK及Caspase-12表达的影响,探讨其对急性胰腺炎保护作用的机制。方法 3月龄SD大鼠96只,随机分为NaCl对照组、TUDCA对照组、CER组、TUDCA治疗组,每组24只。于造模成功后的第0.5、1、2、4 h取胰腺组织,采用常规HE染色法观察各组大鼠胰腺组织学改变;应用免疫蛋白印迹法检测GRP78/BIP、sXBP-1、pJNK及Caspase-12蛋白的表达情况。结果 CER组、TUDCA治疗组均出现炎症反应及凋亡形态学改变,而TUDCA治疗组反应较轻。诱导后各时间点CER组GRP78/BIP呈上升趋势;TUDCA治疗组较比CER组表达降低(P＜0.05),但仍高于NaCl对照组。CER组sXBP-1在诱导后1 h、2 h表达增加,与TUDCA治疗组比较,差异有统计学意义(P＜0.05)。CER组、TUDCA治疗组pJNK的表达于05 h达到峰值,其后呈下降趋势,但仍显著高于NaCl对照组、TUDCA对照组（P＜0.05）,TUDCA治疗组pJNK水平较CER组降低,在时间点2 h、4 h的表达差异有统计学意义（P＜0.05)。CER组Caspase-12的表达增加,于2 h达到峰值。TUDCA治疗组与CER组比较,Caspase-12的表达降低,在时间点0.5 h、1 h、2 h差异有统计学意义（P＜0.05）。结论 TUDCA通过下调GRP78/BIP、sXBP-1,抑制pJNK、Caspase-12表达,发挥其对大鼠急性胰腺炎的细胞保护潜能。     

Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis

OBJECTIVE: To determine the effect of ursodeoxycholic acid (UDCA) in very-low-birth-weight (VLBW) infants with parenteral nutrition-associated cholestasis (PNAC).STUDY DESIGN: A retrospective study of all VLBW infants with PNAC who were admitted to a tertiary referral center was conducted. Patients were classified as treatment group (receiving UDCA within 14 days after onset of cholestasis) or control group (no medical treatment). Patients who received abdominal surgery were excluded. RESULTS: A total of 30 patients were recruited, including 12 in the treatment group and 18 in the control group. The demographic data, total fasting duration, onset of cholestasis, age to tolerance of full feeds, and the duration of parenteral nutrition (PN) before the onset of cholestasis were comparable between the two groups. There was a trend in the control group to later onset of cholestasis. The patients who received UDCA therapy with doses of 10 to 30 mg/kg/day had a shorter duration of cholestasis than the control group (62.8 vs 92.4 days, P=.006). Furthermore, the peak serum levels of direct bilirubin also was significantly lower in the treatment group. CONCLUSION: UDCA can improve the course of PNAC in VLBW infants.     

利用糠醛显色反应测定牛磺熊去氧胆酸含量

牛磺熊去氧胆酸(Tauroursodeoxycholic acid,简称TUDCA)是人及哺乳动物胆汁中存在的天然结合型胆汁酸。在酸性条件下,TUDCA与糠醛反应形成紫色物质,称为Gregory-Pascoe反应,可能是糠醛之羧基与TUDCA分子中羟基缩合成共价化合物之结果。本研究通过对反应物全波长扫描,确定了其最大吸收波长,制定了标准曲线,进行回     

Leptin-based adjuvants: An innovative approach to improve vaccine response

Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥ 30 kg/m²) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin's role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants.     

牛磺熊脱氧胆酸对棕榈酸诱导的INS-1细胞凋亡的保护作用

目的:探讨牛磺熊脱氧胆酸(tauroursodeoxycholic acid,TUDCA)对棕榈酸(palmitate)诱导的INS-1细胞凋亡的保护作用?方法:分别用不同浓度棕榈酸(0.25?0.50?1.00 mmol/L)?棕榈酸(0.50 mmol/L)加TUDCA(100 μmol/L)培养INS-1细胞24 h,用四甲基偶氮唑盐(MTT)法检测细胞活性,流式细胞术检测细胞早期凋亡,Western blot检测内质网应激相关蛋白GRP78的表达?结果:与对照组相比,棕榈酸组(浓度≥0.5 mmol/L)的INS-1细胞凋亡率显著上升(P < 0.05);加TUDCA培养24 h以后,与棕榈酸组相比,INS-1细胞凋亡率显著下降(P < 0.05)?此外,棕榈酸组(0.5 mmol/L)INS-1细胞内质网应激相关蛋白GRP78的表达显著上升(P < 0.05);加TUDCA培养24 h以后,与棕榈酸组相比,INS-1细胞GRP78蛋白表达显著下降(P < 0.05)?结论:TUDCA能够减少游离脂肪酸引起的INS-l细胞凋亡,对INS-1细胞发挥保护作用?而减少内质网应激蛋白的表达,缓解内质网应激可能是其作用机制之一?     

The unfolded protein response in retinal vascular diseases: Implications and therapeutic potential beyond protein folding

Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness.