宁夏无果枸杞芽提取物对自然衰老小鼠学习记忆、MAO、GSH-Px及ChAT活性的影响

目的 观察宁夏无果枸杞芽提取物（FLE）对自然衰老小鼠学习、记忆功能,脑组织中谷胱甘肽过氧化物酶（GSH-Px）、单胺氧化酶（MAO）、乙酰胆碱转移酶（ChAT）的活力的影响,探讨FLE抗衰老机制.方法 将60只13月龄自然衰老昆明小鼠分为老年对照组和FLE低剂量组（FLE1组）、FLE中剂量组（FLE2组）、FLE高剂量组（FLE3组）,每组15只;另将15只6月龄昆明小鼠做为成年对照组.FLE1组、FLE2组、FLE3组分别用质量/体积百分比为5％、10％、20％ FLE灌胃,0.2mL·（10·d）-1,老年对照组和成年对照组灌胃等量生理盐水,连续8周.用Morris水迷宫检测各组小鼠给药前后的学习记忆能力;分光光度法检测脑组织中GSH-Px、MAO和ChAT的活性;免疫组化方法检测小鼠大脑皮层和海马区的ChAT的表达.结果 给药后,与成年对照组比较,老年对照组小鼠逃避潜伏期延长、目标象限停留时间百分比缩短（P＜0.01）,脑组织中MAO活力增高,GSH-Px、ChAT活性降低（P＜0.01）;与老年对照组比较,FLE2组、FLE3组小鼠逃避潜伏期缩短、目标象限停留时间百分比延长（P＜0.01）,FLE3组脑组织中MAO活性降低、GSH-Px活性明显升高（P＜0.01）,FLE2及FLE3组脑组织中ChAT活性增高（P＜0.01）;FLE各组间比较,FLE3组治疗效果较FLE1组及FLE2组好（P＜0.01）.结论 较高浓度的FLE能够改善自然衰老昆明小鼠的学习记忆能力,其机制可能与FLE提高GSH-Px活性,降低MAO活性,发挥抗氧化作用以及上调脑组织中ChAT的活性,提高脑组织中乙酰胆碱含量有关.     

护理干预对还原型谷胱甘肽治疗病毒性肝炎的影响

目的 探讨还原型谷胱甘肽联合综合护理干预治疗病毒性肝炎的效果及应用价值.方法 回顾性分析我院130例病毒性肝炎临床资料,随机分为观察组、对照组各65例,对照组给予护肝片治疗,观察组给予还原型谷胱甘肽治疗,两组同时予护理干预.结果 观察组经治疗和护理后焦虑自评量表评分、抑郁自评量表评分、总胆红素、丙氨酸氨基转移酶、门冬氨酸氨基转移酶、白蛋白等指标均优于对照组（P＜0.05）.观察组治疗依从性、护理满意度均好于对照组（P＜0.05）.结论 综合护理干预能够明显改善患者肝脏功能及焦虑、抑郁不良心理状态,提高临床治疗依从性和护理满意度,应予推广.     

MTHFR基因多态性与儿童支气管哮喘易感性及糖皮质激素疗效的相关性

目的 探讨亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）基因多态性与儿童支气管哮喘易感性及糖皮质激素（glucocorticoid,GC）疗效的相关性。 方法 选取2018年6月至2020年12月住院治疗的儿童支气管哮喘患儿173例为观察组,均接受GC雾化吸入治疗,连续3个月。选取同期体检的健康儿童178例为对照组。采用PCR检测两组受试儿MTHFR基因C677T位点的基因型,分析两组基因型分布差异性;比较观察组不同基因型患儿治疗前后血清免疫球蛋白E、白细胞介素-8（interleukin-8,IL-8）、白三烯B4（leukotriene B4,LTB4）水平,肺功能指标差异及临床疗效差异。 结果 与对照组相比,观察组TT基因型及T等位基因频率均显著升高（P<0.001）;TT/CT基因型及T等位基因是支气管哮喘易感性的独立危险因素（OR分别为6.615、7.055,P<0.001）。GC治疗后3种基因型患儿免疫球蛋白E、IL-8和LTB4水平较治疗前显著降低,第1秒用力呼气容积（forced expiratory volume in 1 second,FEV1）、用力肺活量（forced vital capacity,FVC）、FEV1/FVC%较治疗前显著升高（P<0.001）;TT基因型患儿IL-8和LTB4水平显著低于CC基因型患儿,LTB4水平明显低于CT基因型患儿,TT基因型患儿FVC明显高于CT基因型患儿,FEV1/FVC%显著高于CC基因型患儿（P<0.05）;治疗后3种基因型患儿临床GC治疗疗效比较差异有统计学意义,其中TT基因型患儿GC疗效良好比例显著高于CC基因型患儿（P<0.05）,且TT基因型是GC疗效良好的独立影响因素（OR=2.111,P=0.018）。 结论 MTHFR基因多态性与儿童哮喘易感性及GC疗效相关,携带TT/CT基因型儿童支气管哮喘发病风险更高,TT基因型对GC治疗具有更高的敏感性。     

Association of vitamin D serum levels and its common genetic determinants,with severity of liver fibrosis in genotype 1 chronic hepatitis C patients

Lower 25‐hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome‐wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D‐binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy‐proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high‐pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023–1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974–0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002–1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919–0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106–16.120; P = 0.03), moderate–severe steatosis (OR, 2.588; 95% CI, 1.355–4.943; P = 0.004) and moderate–severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307–4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.     

Effects of Enalapril,Tempol, and Eplerenone on Salt-Induced Hypertension in Dahl Salt-Sensitive Rats

The renin-angiotensin-aldosterone system (RAAS) has been implicated in the pathophysiology of salt-induced hypertension. Angiotensin converting enzyme inhibitors, angiotensin II-type 1 receptor blockers, and aldosterone receptor blockers are used to treat hypertension and congestive heart disease. In addition to their blood pressure lowering effects, they appear to protect against myocardial, renal, and vascular damage. In various models of hypertension, generation of reactive oxygen species is increased in the vasculature and that treatment with antioxidants or superoxide dismutase mimetics (e.g., tempol) improves vascular function and structure and reduces blood pressure. The purpose of this study was to examine the effects of enalapril, an angiotensin II converting enzyme inhibitor; eplerenone, a selective aldosterone receptor antagonist; and tempol, a superoxide dismutase mimetic, on salt-induced hypertension in Dahl Salt-Sensitive rats. The rats were placed on a high salt (HS; 8%) diet for 3 weeks prior to switching to a normal salt (0.3%) diet for an additional 3 weeks. While on the normal salt (NS) diet, rats were treated with enalapril (30 mg/kg/day in the drinking water), eplerenone (100 mg/kg/day by gavage), tempol (1 mM/day in the drinking water), eplerenone + enalapril, eplerenone + enalapril + tempol, or without drug treatment (control). After 3 weeks on HS diet, systolic blood pressure rose from 127 ± 7 to 206 ± 11 mm Hg and remained elevated when switched to NS diet. Subsequently, treatment with eplerenone alone or in combination with enalapril and tempol produced a stepwise reduction in systolic blood pressure reaching ?80 mm Hg; however, enalapril and tempol alone produced more modest pressure reduction (～?35 mmHg). Plasma levels of prostacyclin and nitric oxide were elevated in rats treated with enalapril and eplerenone alone or in combination. Enalapril and eplerenone alone and in combination reduced heart and kidney levels of angiotensin II and aldosterone when compared with control. Renal and heart levels of reduced glutathione were diminished by eplerenone alone; however, enalapril tended to attenuate the effect of eplerenone on reduced glutathione levels in the heart. The findings from this study suggest that eplerenone reduces salt-induced hypertension by increasing endothelium-derived relaxing factors, inhibiting RAAS components and oxidative stress. (353words)     

Rosuvastatin: a new inhibitor of HMG-CoA reductase for the treatment of dyslipidemia

Rosuvastatin (Crestor^®, AstraZeneca) is a synthetic statin that represents an advance on the pharmacologic and clinical properties of other agents in this class. Relative to other statins, rosuvastatin possesses a greater number of binding interactions with HMG-CoA reductase and has a high affinity for the active site of the enzyme. Rosuvastatin is relatively hydrophilic and is selectively taken up by, and active in, hepatic cells. Rosuvastatin has the longest terminal half-life of the statins and is only minimally metabolized by the cytochrome P450 (CYP 450) enzyme system with no significant involvement of the 3A4 enzyme. Consistent with this finding is the absence of clinically significant drug interactions between rosuvastatin and other drugs known to inhibit CYP 450 enzymes. In patients with hypercholesterolemia, rosuvastatin 10–40 mg has been shown to reduce low-density lipoprotein cholesterol (LDL-C) levels by 52–63%, as well as increase high-density lipoprotein cholesterol (HDL-C) levels by up to 14% and reduce triglycerides (TG) by up to 28%. Studies have shown that rosuvastatin is superior to atorvastatin, simvastatin and pravastatin in reducing LDL-C and favorably modifying other components of the atherogenic lipid profile. The significant decreases in LDL-C with rosuvastatin treatment should help to improve attainment of lipid goals and reduce the requirement for dose titration. In addition, the effects of rosuvastatin on HDL-C and TG levels will be of benefit in treating patients with abnormalities such as mixed dyslipidemia and the metabolic syndrome. Rosuvastatin is well tolerated, with a safety profile comparable with that of other currently available statins.     

Expression of the homeostasis-related markers,maspin, heat shock proteins 70 & 90, glutathione S-transferase,aquaporin 5 and NF-kB in young and old labial and palatal salivary glands

Intraoral salivary glands undergo remarkable age-related morphologic changes. This study investigated the expression of a panel of molecular markers known for cellular homeostatic activity, dependent on age and location of the salivary glands. Samples taken from healthy subjects were classified according to age (“young” < 45 years, n = 51, and “old” ≥ 60 years, n = 45) and location (lip, n = 47 and palate, n = 49). They were immunohistochemically stained for mammary serine protease inhibitor (maspin), heat shock protein (HSP)70, HSP90, glutathione S-transferase (GST), aquaporine5 (AQP5), and nuclear factor kappa-B (NF-κB) for assessment of their expression in acini and ducts, and in cytoplasmic and nuclear compartments. Results were expressed as the mean percentage of positively stained component per age group, gland location and type of cell and cellular compartment. Statistical analysis was performed by two-way ANOVA and crosstabs. The expression of maspin was lower in the old group in both the palatal and labial glands (acini and ducts, cytoplasm and nuclei) compared to the young group (p < 0.05). In both age groups, when compared to labial glands, palatal glands exhibited higher expression of HSP70 (p < 0.05) and lower expression of AQP5 (p < 0.001) and NF-κB (p = 0.018). Collectively, the low expression of factors capable of preserving cellular homeostasis (i.e., maspin and AQP5) vis-à-vis a high expression of factors that are also related to cell survival (i.e., HSPs) that was demonstrated in the old palatal glands may point to their high vulnerability to undergo selective phenotypic changes.