Effect of sacubitril/valsartan on the expression of Gal-3 and MMP-9 in rabbits with cardiac hypertrophy

Objective:To investigate the effects of sacubitril/valsartan on the expression of Galectin-3 (Gal-3) and Matrix metalloproteinase-9 (MMP-9) in New Zealand rabbits with stress-induced cardiac hypertrophy.Methods: Twenty-four healthy male 8-week-old New Zealand rabbits were randomly divided into sham operation group (Sham), model group (Model), and sacubitril/valsartan group (Sacu/Vals), with 8 rats in each group. Abdominal aortic coarctation was used to construct a model of cardiac hypertrophy. After 8 weeks of successful modeling, the acubitril/valsartan group was administered with the drug, and the other two groups were given an equal volume of normal saline. All rabbit hearts were sacrificed at the end of the 16th week. The left ventricular mass index and the whole heart mass index were measured. The left ventricular myocardial tissue was evaluated by HE staining to evaluate the cardiac hypertrophy. The expression of Gal-3 and MMP-9 in the myocardial tissue was detected by western blot.Results: (1) Compared with the sham operation group, the HMI and LVMI of the model group and the sacubitril/valsartan group increased. Compared with the model group, the HBA and LVMI decreased in the sacubitril/valsartan group;(2) In the sham operation group, the myocardial fibers were arranged neatly, arranged in a bundle, and the morphology was intact, and no obvious fibrous tissue was observed. The myocardial fibers in the model group were disordered, most of them were broken, the cells were edematous, and the myocardial interstitial showed fibrous connective tissue. Compared with the model group, the sacubitril/valsartan group had a neat arrangement of myocardial fibers and a significant reduction in cell edema;(3) Compared with sham operation, the expression of Gal-3 and MMP-9 protein in the model group and the sacubitril/valsartan group increased;compared with the model group, sacubitril/valsartan the expression levels of Gal-3 and MMP-9 in the tan group were decreased.Conclusion: Sacubitril/valsartan can alleviate cardiac hypertrophy in rabbits, and its mechanism may be related to down-regulation of Gal-3 and MMP-9 protein expression.

强直性脊柱炎患者血清骨桥蛋白及基质金属蛋白酶-3检测临床意义研究

目的探讨强直性脊柱炎(AS)患者血清骨桥蛋白(OPN)及基质金属蛋白酶-3(MMP-3)水平的变化及其临床意义。方法采用酶联免疫吸附法检测并比较50例AS患者及20例健康者血清OPN及MMP-3水平,并与患者血细胞沉降率(ESR)、C反应蛋白(CRP)水平进行相关分析。结果 AS患者血清OPN水平明显高于健康者(P<0.05),且与患者ESR及CRP水平呈正相关(P<0.05);AS患者血清MMP-3水平明显高于健康者(P<0.05),且与患者ESR、CRP水平呈正相关(P<0.05);AS患者血清OPN水平与MMP-3水平呈正相关(P<0.05)。结论 OPN及MMP-3参与AS发病,其血清水平检测可用于患者病情活动判断及疗效评价。

金天格胶囊对绝经后膝骨关节炎OPN和MMP3表达的影响

目的探讨金天格胶囊对绝经后膝骨关节炎患者血清中骨桥蛋白(OPN)和基质金属蛋白酶3(MMP-3)表达的影响。方法 2013年1月-12月将180例绝经后膝骨关节炎妇女随机分为金天格胶囊组(A组)、盐酸氨基葡萄糖胶囊组(B组)、仙灵骨葆胶囊组(C组),每组60例,采用酶联免疫吸附试验测定各组血清MMP-3、OPN、雌二醇(E2)、Ⅰ型胶原C端肽(CTX)和Ⅰ型胶原N端前肽(PINP)水平。结果 A组和B组在治疗后4周和6周JOA和VAS评分明显优于C组(P<0.05),B组在治疗后4周的MMP-3表达改善明显(P<0.05),优于其他两组。治疗后6周,A组OPN和MMP-3表达水平改善明显(P<0.05),优于其他两组。同时,A组和C组CTX和PINP水平明显改善(P<0.05),优于B组。结论金天格胶囊能有效改善绝经后骨性关节炎的症状,可能通过调节OPN和MMP3的复合体表达,改善关节软骨的功能实现这一目的。

Effects of (-)-epigallocatechin-3-gallate on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibroblasts irradiated with ultraviolet A

Background It is known that ultraviolet irradiation can affect cellular function through a number of signaling pathways ( ) epigallocatechin 3 gallate (EGCG) is the major effective component in green tea and can offer protection from ultraviolet induced damage In this study, we investigated the protective mechanism of EGCG on human dermal fibroblasts damaged by ultraviolet A (UVA) in vitro Methods Transcription factor Jun protein levels were measured by Western blot Matrix metalloproteinase 1 (MMP 1) and tissue inhibitor of metalloproteinase 1 (TIMP 1) mRNA were studied by reverse transcription polymerase chain reaction (RT PCR) analysis in conjunction with computer assisted image analysis MMP 1 and TIMP 1 proteins were quantified by enzyme linked immunosorbent assay (ELISA) Results EGCG decreased transcription activity of Jun protein after induction by UVA Both the mRNA and protein levels of MMP 1 were increased by UVA irradiation, while no significant changes were observed in TIMP 1 levels The ratio of MMP 1 to TIMP 1 showed statistically significant differences compared with the control EGCG decreased the ratio of MMP 1 to TIMP 1 by inhibiting UVA induced MMP 1 expression ( P <0 05) Conclusion EGCG can protect human fibroblasts against UVA damage by downregulating the transcription activity of Jun protein and the expression of MMP 1 The ratio of MMP 1 to TIMP 1, rather than the levels of MMP 1 or TIMP 1 alone, may play a significant role in human skin photodamage

Alzheimer's disease with sleep insufficiency:a cross-sectional study on correlations among clinical characteristics,orexin,its receptors,and the bloodbrain barrier

Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.

Expression of matrix metallo-proteinase-28 in human normal cytotrophoblast cells and a choriocarcinoma cell line,JEG-3

There are striking similiarities present between the behavior of invasive placentaL cells and that of invasive cancer cells. Matrix metalloproteinases (MMPs) are one of the most important mediators. MMP-28, the new member of MMPs, was sequenced and identified recently. Expression of MMP-28 mRNA and protein in the cytotrophoblast cells and a choriocarcinoma cell line, JEG-3 cell, was conducted by zymography, RT-PCR and Northern blot. There is MMP-28 mRNA expression in both the cytotrophoblast cells and JEG-3 cells by RT-PCR. The activity of MMP-28 in cytotrophoblast cells was significantly weaker than that in JEG-3 (P 【 0.01) by zymography. Furthermore, mRNA expression of MMP-28 was significantly stronger (P 【 0.001) in JEG-3 than in human cytotrophoblast cells in a time-dependent way by Northern Blot. Our results suggest that MMP-28 may play a role in some of the tissue-remodeling events associated with normal pregnancy and tumor progression.

活动期类风湿关节炎患者血清基质金属蛋白酶-3及其组织抑制剂-1水平的检测和意义

目的研究活动期类风湿关节炎(rheum atoid arthritis,RA)患者血清基质金属蛋白酶-3(m atrix m etalloproteinase3,M M P-3)、金属蛋白酶组织抑制剂-1(tissue inhibitors ofm etalloproteinase1,TIM P-1)的水平及其相关影响因素,探讨M M P-3及TIM P-1在R A的作用机制。方法选择41例初诊活动期RA患者和30名正常健康志愿者,以酶联免疫吸附试验(ELISA)分别检测血清M M P-3及TIM P-1水平,计算M M P-3/TIM P-1,同时测定关节功能、X线、关节肿胀数(SJC)、血沉(ESR)、类风湿因子(R F)、C反应蛋白(CR P)等相关实验室指标。结果活动期R A患者血清M M P-3、TIM P-1明显增高(P<0.01),且以M M P-3增高更为显著,M M P-3/TIM P-1较正常组亦增高(P<0.05)。不同关节功能分级时,上述指标差异无统计学意义(P>0.05),而不同X线分期时,各指标差异有统计学意义(P<0.01或P<0.05)。M M P-3、M M P-3/TIM P-1与SJC(P<0.01)、CRP(P<0.01)、ESR(P<0.05)呈正相关,二者与年龄、病程、晨僵时间、RF无明显相关性(P>0.05)。结论M M P-3、TIM P-1在RA血清中高水平存在,二者比例失衡导致RA发生。M M P-3、M M P-3/TIM P-1的高低可作为反映病情活动及预后的指标,阻断M M P-3高水平有可能成为治疗RA的新途径之一。

Effects of Weipixiao(胃痞消)on Wnt Pathway-Associated Proteins in Gastric Mucosal Epithelial Cells from Rats with Gastric Precancerous Lesions*

Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.