Experimental Study on Inhibitory Effect of Niacinamide on Tumor Necrosis Factor-alpha-induced Matrix Degradation of Annulus Fibrous Tissue in vitro

The inhibitory effect of niacinamide on tumor necrosis factor-α （TNF-α） induced annulus fibrous （AF） degradation was assessed, and the mechanism of the inhibition was investigated. Chiba＇s intervertebral disc （IVD） culture model was established. Forty-eight IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups （12 IVDs in each group）, and various concentrations of niacinamide and TNF-α were added to the medium for intervention： negative control group, niacinamide control group （0.5 mg/mL niacinamide）, degeneration group （10 ng/mL TNF-α）, and treatment group （0.5 mg/mL niacinamide and 10 ng/mL TNF-α）. After one week＇s culture, AFs were collected for glycosaminoglycan （GS） content measurement, safranin O-fast green staining, and immunohistochemical staining for type Ⅰ , Ⅱ collagen and cysteine containing aspartate specific prote- ase-3 （Caspase-3）. It was found that the GS content in treatment group was increased by about 48% as compared with degeneration group （t=16.93, P〈0.001）, and close to that in niacinamide control group （t=0.71, P=0.667）. Safranine O-fast green staining exhibited higher staining density and better histological structure of AF in the treatment group as compared with the degeneration group. Immunohistochemical staining for both TypeⅠ and Ⅱ collagen demonstrated that lamellar structure and continuity of collagen in treatment group were better reserved than in degeneration group. Positive staining rate of Caspase-3 in AFs of negative control group, niacinamide control group, degeneration group and treatment group was 3.4%, 4.3%, 17.9% and 10.3% respectively. The positive rate in treatment group was significantly lower than in degeneration group （P〈0.01）. It was concluded that niacinamide could effectively alleviate TNF-α induced destruction and synthesis inhibition of matrix ingredients in AFs. The inhibition may be related with reduction of expression of Caspase-3. Thus, niacinamide is of potential f     

Up-regulation of Niacinamide in Intervertebral Disc Aggrecan in vitro

The regulatory effects of niacinamide （Nia） on intervertebral disc （IVD） aggrecan in vitro was investigated. Chiba＇s 10 ng/mL interleukin-1 （IL-1）-induced rabbit IVD degeneration model in vitro was established. 0.5, 0. 25 and 0.05 mg/mL Nia was added to normal and degenerated IVDs for intervention. On the first and second week after intervention, safranin O-fast green staining intensity and glycosaminoglycan （GS） content were measured. The expression of aggrecan core protein was detected by RT-PCR. The results showed： （1） After treatment with 0. 5 mg/mL Nia for one week, the GS content in nucleus pulposus （NP） was increased by 44.80% as compared with control group （P〈0. 01） ; The GS content in IL-1 induction groups was increased with the increase of Nia concentrations： After treatment with 0. 5 mg/mL for one week, the GS content in NP was increased by 68.30% as compared with control group （P〈0. 01）. After two weeks, GS content in NP and fibrous rings was still higher than in control group at the same period （P〈0. 01） and untreated group （P〈0.01）. （2） Safranin O-fast green staining revealed that with the increase of Nia concentrations, staining density in NP and fibrous rings was increased and histological structure damage to IVDs by IL-1β was alleviated. （3） RT-PCR showed that the expression of core protein gene in IL-1β-induced degenerated IVDS was increased with the increase of Nia concentrations. It was concluded that under conditions in vitro, Nia could up-regulate the expression of aggrecan in IVDs and protect IVDs from IL-1β-induced degeneration at least partially, which offers a potential choice for IVD degeneration clinical therapy.     

Differentiation of adipose-derived stem cells towards nucleus pulposus-like cells induced by hypoxia and three-dimensional chitosan-alginate gel scaffold in vitro

Background Injectable three-dimensional (3D) scaffolds have the advantages of fluidity and moldability to fill irregular-shaped defects, simple incorporation of bioactive factors, and limited surgical invasiveness. Adipose-derived stem cells (ADSCs) are multipotent and can be differentiated towards nucleus pulposus (NP)-like cells. A hypoxic environment may be important for differentiation to NP-like cells because the intervertebral disc is an avascular tissue. Hence, we investigated the induction effects of hypoxia and an injectable 3D chitosan-alginate (C/A) gel scaffold on ADSCs. Methods The C/A gel scaffold consisted of medical-grade chitosan and alginate. Gel porosity was calculated by the liquid displacement method. The pore microstructure was analyzed by light and scanning electron microscopy. ADSCs were isolated and cultured by conventional methods. Passage 2 BrdU-labeled ADSCs were co-cultured with the C/A gel. ADSCs were divided into three groups (control, normoxia-induced, and hypoxia-induced groups). In the control group, cells were cultured in 10% FBS/DMEM. Hypoxia-induced and normoxia-induced groups were induced by adding TGF-β1, dexamethasone, vitamin C, sodium pyruvate, proline, bone morphogenetic protein-7, and 1% ITS-plus to the culture medium and maintained in 2% or 20% O2, respectively. Histological and morphological changes were observed by light and electron microscopy. ADSCs were characterized by flow cytometry. Cell viability was investigated by BrdU incorporation. Proteoglycan and type II collagen were measured by safranin O staining and the Sircol method, respectively. mRNA expression of hypoxia inducing factor-1α (HIF-1α), aggrecan, and type II collagen was determined by RT-PCR. Results C/A gels had porous exterior surfaces with 80.57% porosity and 50–200 μm pore sizes. Flow cytometric analysis of passage 2 rabbit ADSCs showed high CD90 expression, while CD45 expression was very low. The morphology of induced ADSCs resembled that of NP cells. BrdU immunofluorescence showed that most ADSCs survived and proliferated in the C/A gel scaffold. Scanning electron microscopy showed that ADSCs grew well in the C/A gel scaffold. ADSCs in the C/A gel scaffold were positive for safranin O staining. Hypoxia-induced and normoxia-induced groups produced more proteoglycan and type II collagen than that in the control group (P <0.05). Proteoglycan and type II collagen levels in the hypoxia-induced group were higher than those in the normoxia-induced group (P <0.05). Compared with the control group, higher mRNA expression of HIF-1α, aggrecan, and type II collagen was detected in hypoxia-induced and normoxia-induced groups (P <0.05). Expression of these genes in the hypoxia-induced group was significantly higher than that in the normoxia-induced group (P <0.05). Conclusions ADSCs grow well in C/A gel scaffolds and differentiate towards NP-like cells that produce the same extracellular matrix as that of NP cells under certain induction conditions, which is promoted in a hypoxic state.     

Pathological study on right atrium myocardium in rheumatic heart dis-ease patients with atrial fibrillation

Objective: To study the pathological basis of right atrial fibrillation in rheumatic heart disease (RHD) patients with atrial fibrillation (AF). Methods: Twenty-nine patients with mitral valve replacement of RHD were divided into AF group (n=13) and sinus rhythm group (SN group) (n=16). There was no significant statistical difference in clinical factors between the 2 groups. During the operation of valve replace-ment, the samples of right atrial appendages were taken and the qualitative and quantitative study were made by light microscopy and electron microscopy. Results: (1) Light microscope: The interstitial fibrosis and the arrangement of myocardium was more disordered in AF group than that in SN group. However, no statistic difference was found in interstitial fibrosis and cellar hypertrophy degree between the 2 groups. (2) Electron microscope: Mitochondrial crosta broke and dissolved obviously in AF group. The mitochondrial volume in AF group was smaller than that in SN group. Volume density, average area and average perimeter in AF group were less than that in SN group ; specific surface in AF group was bigger than that in SN group. There was significant difference of above factors between the 2 groups; but there was no significant difference of surface density and numerical density on area in the 2 groups. Volume density of myofibril in AF group and SN group were less than that in SN group. (3)Split of Intercalated disc(ID) gap was found in AF group, and there was marrowing and floccular substance in ID gap. Conclusion : There were significant differences in the pathological changes of right atrial myocardium between AF and SN with RHD, these changes may be the im-portant pathological basis for RA fibrillation of AF patients with RHD.     

Apoptosis, myocardial fibrosis and angiotensin Ⅱ in the left ventricle of hyp ertensive rats treated with fosinopril or losartan

Objective To investigate the different effects of an angiotensin Ⅱ type 1 (AT(1)) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin Ⅱ (AngⅡ) in the left ventricle of spontaneously hypertensive rats (SHRs). Methods SHRs of 16-week-old were randomly divided into 3 groups: SHR-L (treated with losartan, 30 mg·kg(-1)·d(-1)), SHR-F (treated with fosinopril, 10 mg·kg(-1)·d(-1)), and SHR-C (treated with placebo). Each group consisted of 10 rats. Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment. Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and AngⅡ concentrations of plasma and myocardium were examined. Results Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups. Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups. However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group. Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups. The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined. Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan. However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group. Compared with the controls at endpoints, plasma and myocardium Ang Ⅱ levels were significantly increased in the losartan group. However, plasma Ang Ⅱ concentrations were not altered, and myocardium AngⅡ concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group. Conclusions Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin-angiotension-aldsterone system.     

The remedial effect of soluble interleukin-1 receptor type II on endometriosis in the nude mouse model

Objective: Recent studies have shown that the local expression of soluble interleukin (IL) -1 receptor type Ⅱ (sIL-1 RⅡ) in endometrial tissue of women with endometriosis is decreased, and the depression of IL-1 RⅡ was more significant in infertile women than that in fertile women with endometriosis. In this research, we investigated the remedial effect of sIL-1-RⅡ administration on endometriosis in the nude mouse model. Methods: Nineteen nude model mice with endometriosis were randomly divided into three groups: group A was treated by intraperitoneal administration with only sIL-1 RⅡ for two weeks, group B was similarly treated with only IL-1, and group C (control) was administered saline . After 2 weeks, the size of the ectopic endometrial lesions was calculated, and the expression of vascular endothelial growth factor (VEGF) and B-cell lymphoma leukemia-2 (Bcl-2) were detected by immunohistochemistry. The IL-8 and VEGF levels in the peritoneal fluid (PF) and serum were also measured by enzyme-linked immunosorbent assay (ELISA). Results: The mean size of ectopic endometrial lesion did not differ between the three groups (P > 0.05). Compared with the control, the expression of VEGF and Bcl-2 was significantly lower in group A, and higher in group B. In the three groups, the levels of IL-8 in the PF and serum were highest in group A, and lowest in group B. Conclusion: sIL-1 RⅡ may suppresse hyperplasia of ectopic endometriosis, perhaps by reducing the expression of certain cytokines, such as VEGF, IL-8, and Bcl-2, which could provide a new clinical strategy for the treatment of endometriosis.     

Chinese Herbal Formula Ermiao Powder (二妙散) Regulates Cholinergic Anti-inflammatory Pathway in Rats with Rheumatoid Arthritis

Objective: To investigate the effect of Chinese herbal formula Ermiao Powder (二妙散, EMP) on the expression of cholinergic anti-inflammatory pathway in rats with rheumatoid arthritis (RA). Methods: Seventy two rats were randomly ivided into 6 groups according to body weight, including normal control group, collagen induced arthritis (CIA) group, three doses EMP groups, and methotrexate (MTX) group (n=12 per group). All of the rats except for those in the normal control group were given multipoint subcutaneous injection of bovine type Ⅱ collagen to establish a CIA model. Three EMP groups received a high- (4.5 g/kg), medium- (3.0 g/kg), and low- (1.5 g/kg) doses of EMP by intragavage, respectively. MTX group was injected intraperitoneally MTX at 0.9 mg/kg once a week as the positive control. The administration was 3 consecutive weeks. Joint swelling, arthritis index, and body weight changes in different experimental groups of rats were tested. The joint damage was evaluated by masson staining. Quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry (IHC) were performed to evaluate the expression of CHRNA7, encoding α 7 nicotinic acetylcholine receptor in the cholinergic anti-inflammatory pathway, in different tissues and their localization in the spleen and joints. Results: CHRNA7 expression levels were significantly higher in the joints and spleens of CIA group than those in normal control group (both P<0.05). Moreover, the CHRNA7 mRNA and protein levels in the spleen and joints of MTX and three doses of EMP groups were significantly lower than CIA group (all P<0.05). Compared with the MTX group, treatment with low-dose EMP resulted in significant reduction of CHRNA7 mRNA and protein expression levels (P<0.05 or P<0.01). IHC showed positive signals of CHRNA7 in the white pulp and red pulp of the spleens of rats; CHRNA7 was expressed on fibroblast-like synoviocytes, macrophages, and endothelial cells in the joints of rats, and the expression in the joints of low-dose EMP group was significantly lower than that in the CIA group (P<0.01). Conclusion: Cholinergic anti-inflammatory pathway was involved in the generation of the inflammatory reaction in CIA rats, and EMP exerted therapeutic effect on RA through cholinergic anti-inflammatory pathway.     

Effects of Calcium Dobesilate on Glomerulus TIMP1 and Collagen Ⅳ of Diabetic Rats

Summary ： To observe the effects of calcium dobesilate on the expression of glomerular tissue inhibitor of metalloproteinase 1 （TIMP1）, collagen Ⅳ , and ultrastrueture of glomerular basement mem- brane in diabetic rats, rats model of diabetes was established by unilateral nephreetomy and intraperitoneal injection of 1% STZ （55 mg/kg）, and rats were administered calcium dobesilate 100 mg/ kg （DD group） or distilled water （DM group） respectively. 12 weeks later, the changes in the renal uhrastrueture and ereatinine clearance rate （Cer） were examined in each group. The expression of glomerular TIMP1 and collagen Ⅳ were studied by immunohistoehemieal staining. Our results showed that after 12 weeks, the Cer in DD group increased and was significantly higher than that in DM group. Electron microscopy showed that thickness of glomerular capillary basement membrane （GBM） in Group DD was less than that of DM group. No hyperplasia of collagen fibers was found, and the distance betweeh the holes of endothelial cells in DD group was not as even as that in the normal group, but more even than that of DM group, and podocyte processes was still in order. Immunohistochemical staining of glomeruli showed that expression of TIMP1 and collagen Ⅳ in DD group were significantly less than those of DM group DM. It is concluded that calcium dobesilate can improve diabetic nephropathy by inhibiting the overaccumulation of collagen Ⅳ and calcium dobesilate may also contribute to diabetes by inhibiting the expression of TIMP1.     

Clinical Observation on Cervical Spondylopathy of the Vertebroarterial Type Treated by Electro-acupuncture

Objective: To observe the clinical therapeutic effects of electro-acupuncture in the treatment of cervical spondylopathy of the vertebroarterial type. Methods: According to the consulting order, the patients were randomly divided into a treatment group (29 cases treated with electro-acupuncture), and a control group (28 cases treated with simple acupuncture). 20 treatments were given to patients in both groups. Results: The markedly effective rate of the treatment group was 75% and that of the control group was 61.54% (P<0.05). Conclusion: Electro-acupuncture has a better therapeutic effect than the simple acupuncture in the treatment of cervical spondylopathy of the vertebroarterial type.     

川芎嗪对IL-1β诱导的兔原代软骨细胞iNOS表达和NO合成的影响

目的观察川芎嗪(tetramethylpyrazine,TMP)对IL-1β(interleukin-1β,IL-1β)诱导的兔原代软骨细胞诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达及一氧化氮(NO)合成的影响。方法体外培养兔软骨细胞,用甲苯胺蓝染色检测蛋白多糖,免疫荧光检测兔原代软骨细胞Ⅱ型胶原;用IL-1β10 ng/ml和(或)不同浓度(5、10、15、20μg/ml)川芎嗪共培养兔原代软骨细胞48 h后,RT-PCR和免疫组化检测iNOS基因及蛋白表达;用硝酸还原法检测细胞培养上清液NO的表达。结果软骨细胞呈三角形或多角形,蛋白多糖表达于细胞质中,Ⅱ型胶原主要表达于细胞质,少见于细胞核。与对照组比较,IL-1β单独作用软骨细胞iNOS和NO的表达显著增加(P<0.01);IL-1β和川芎嗪联合作用后,软骨细胞iNOS和NO的表达较IL-1β单独作用显著降低(P<0.05,P<0.01),但仍显著高于对照组(P<0.01)。结论川芎嗪能有效抑制IL-1β诱导兔软骨细胞iNOS的表达和NO的合成。     

烟酰胺对压力致兔腰椎间盘退变的保护作用

目的 考察烟酰胺对压力诱发的兔腰椎间盘退变的保护作用.方法 取24只日本大白兔随机分入1～6组,采用可控轴向压力致兔腰椎间盘退变模型,以98 N压力诱发椎间盘退变,并按分组要求灌胃给予烟酰胺:第1组2只,安装加压装置不予加压或给药;第2组2只,给予50 mg/(kg·d)烟酰胺灌胃1周;第3组5只,以98 N压力加压1周;第4组5只,以98 N压力加压1周,去除压力自行恢复1周;第5组5只,加压1周,去除压力后给予50 mg/(kg·d)烟酰胺灌胃1周;第6组5只,加压1周,去除压力后恢复1周,自加压开始时持续给予50 mg/(kg·d)烟酰胺灌胃2周.Thompson分级法及腰椎间盘磁共振成像(MRI)评价退变程度;苏木精-伊红染色、Ⅱ型胶原免疫组化染色及藏红O-快绿染色观察其组织学改变;P161NK4A免疫组化染色检测细胞增殖和衰老状态的变化.结果 ①第2组椎间盘未见明显退变;第3组5只动物Thompson分级均为Ⅱ级,第4组4只为Ⅱ级,1只为Ⅲ级,第5组2只为Ⅰ级,3只为Ⅱ级,第6组3只为Ⅰ级,2只为Ⅱ级.MRI也显示.服用烟酰胺的动物椎间盘退变程度有所减轻.②Ⅱ型胶原免疫组化染色显示,第6组纤维环Ⅱ型胶原含量较第4组高约53.2%(P<0.01).③第2组藏红O染色强度较第1组有所上升;第5,6组髓核和纤维环染色强度均高于第4组的相对应部位,其中以第6组髓核染色强度上升最为明显(均P<0.01).④P161NK4A免疫组化显示,P161NK4A阳性率随烟酰胺给药时间延长而降低.结论 烟酰胺有助于减轻压力对椎间盘的损伤,能够促进压力损伤后的椎间盘恢复.     

葛根汤与桂枝汤对兔颈椎间盘组织IL-1β、iNOS、TNFα、TGFβ mRNA表达的调节作用

目的　检测兔动物模型风寒湿颈椎病组、低头位颈椎病组、风寒湿加低头位颈椎病组的颈椎间盘组织中白细胞介素1β(interleukin 1β ,IL 1β)、诱导型氮氧化物合酶 (induciblenitric oxidesynthase,iNOS)、肿瘤坏死因子α(tumornecrosisfactor al pha ,TNFα)、转化生长因子 β(transforminggrowthfactor beta ,TGFβ)的mRNA的表达 ,并检测葛根汤、桂枝汤对兔风寒湿颈椎病组颈椎间盘组织中上述细胞因子mRNA的调节作用。方法　 36只大白兔随机分为正常对照组、风寒湿颈椎病组、低头位颈椎病组、风寒湿加低头位颈椎病组、葛根汤治疗组、桂枝汤治疗组。葛根汤、桂枝汤治疗组均以风寒湿颈椎病模型为基础。采用逆转录聚合酶链反应法检测颈椎间盘组织中上述细胞因子mRNA的表达。结果　各模型组与正常对照组比较IL 1βmRNA、iNOSmRNA表达上调 (P <0 .0 1) ;葛根汤、桂枝汤治疗组与风寒湿颈椎病组比较 ,IL 1βmRNA、iNOSmRNA表达均下调 (P <0 .0 5或 <0 .0 1) ;低头位加风寒湿颈椎病组TNFαmRNA表达上调 ,与风寒湿及低头位颈椎病组比较 (P <0 .0 1) ;葛根汤下调TNFαmRNA表达 ,与风寒湿颈椎病组比较 (P <0 .0 1) ;各模型组同正常对照组比较 ,TGFβmRNA表达均下调(P <0 .0 1) ;与风寒湿颈椎病组比较 ,葛根汤上调TGF     

二十二碳六烯酸对房颤大鼠心房纤维化的影响

目的:探讨二十二碳六烯酸（docosahexaenoic acid,DHA）对大鼠心房颤动模型心房纤维化的影响,及其对细胞外信号调节激酶1/2（extracellular signal-regulated kinase 1/2,ERK1/2）蛋白、磷酸化细胞外信号调节激酶1/2（phosphorylated extracellular signal-regulated kinase 1/2,p-ERK1/2）蛋白、Ⅰ型胶原mRNA和蛋白表达的影响。方法:将80只乙酰胆碱-氯化钙混合液敏感大鼠随机分为对照组（CTL组）、对照DHA处理组（DHA组）、房颤组（AF组）和房颤DHA处理组（DHA+AF组）,各20只。观察各组大鼠房颤持续时间,采用Masson染色法观察大鼠心房组织胶原纤维增生情况,应用Real-time PCR法测定大鼠心房组织中Ⅰ型胶原mRNA表达,Western blot法测定大鼠心房组织中Ⅰ型胶原、ERK1/2和p-ERK1/2蛋白表达。结果:实验第10、17天,DHA+AF组大鼠房颤持续时间均明显短于AF组（P<0.01）。与CTL组比较,AF组大鼠心房肌间质可见大量胶原纤维增生,心房纤维化程度高;DHA+AF组大鼠心房肌间质可见少量胶原纤维增生,心房纤维化程度较AF组降低。与CTL组比较,AF组大鼠P-ERK1/2与ERK1/2比值升高（P<0.05）,DHA组比值降低（P<0.05）,而CTL组与DHA+AF组差异无统计学意义（P>0.05）;与AF组比较,DHA组和DHA+AF组与P-ERK1/2与ERK1/2比值均降低（P<0.05）。与CTL组比较,AF组和DHA+AF组大鼠心房组织Ⅰ型胶原mRNA和蛋白表达水平均升高（P<0.05~P<0.01）;与AF组比较,DHA+AF组大鼠心房组织Ⅰ型胶原mRNA和蛋白表达水平均降低（P<0.05）。结论:DHA具有改善SD大鼠房颤模型心房纤维化的作用,此作用与其抑制心房组织ERK1/2通路的活性进而下调心房组织Ⅰ型胶原mRNA和蛋白的表达有关。     

白细胞介素-17 对脱氧皮质酮/ 盐诱导的高血压 心肌纤维化大鼠巨噬细胞极化的影响

目的 探讨脱氧皮质酮（DOC）/ 盐诱导的高血压心肌纤维化（MF）大鼠中白细胞介素-17（IL-17） 对巨噬细胞极化的作用。方法 30 只雄性清洁级SD 大鼠予右肾切除处理,术后用含0.1% 氯化钾和1% 氯 化钠的饮水灌胃2 周,随机分成对照组、DOC 组、DOC+IL-17 抗体组。使用尾套法测量大鼠动脉收缩压, 1 次/2 周;天狼猩红染色法检测心肌间质纤维化程度;免疫组织化学法观察心肌组织CD11c、CD206 表 达;逆转录聚合酶链反应检测诱导性一氧化氮合酶（iNOS）、精氨酸酶1（Arg1）mRNA 的表达;Western blotting 检测各组IL-17、iNOS 和Arg1 蛋白表达。结果 各组收缩压比较,差异有统计学意义（P <0.05）。 DOC 组心肌间质胶原面积/ 视野总面积比值较对照组增加（P <0.05）;使用IL-17 抗体中和干预治疗后, DOC+IL-17 抗体组心肌间质胶原面积/ 视野总面积比值较DOC 组减少（P <0.05）。DOC 组iNOS、Arg1 mRNA 相对表达量和IL-17、iNOS、Arg1、CD11c、CD206 蛋白相对表达量较对照组升高（P <0.05）,使用 IL-17 抗体中和后,DOC+IL-17 抗体组iNOS、Arg1 mRNA 相对表达量较DOC 组降低（P <0.05）,IL-17、 iNOS、Arg1、CD11c 和CD206 蛋白相对表达量较DOC 组降低（P <0.05）。结论 DOC/ 盐诱导的高血压 大鼠MF 中巨噬细胞极化很可能与IL-17 有关。     

肿瘤坏死因子α和白介素1β及诱导型一氧化氮合酶的表达与幽门螺杆菌相关性胃炎的关系

目的 探讨胃黏膜组织中肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)及诱导型一氧化氮合酶(iNOS)的表达水平与幽门螺杆菌(Helicobacter pylori,Hp)相关性胃炎的关系.方法 选择248例慢性胃炎患者,其中Hp阳性慢性胃炎患者126例(Hp阳性组),Hp阴性慢性胃炎患者122例(Hp阴性组).通过组织学方法评定胃黏膜病理组织学改变,采用快速尿素酶试验及改良Giemsa染色法对受检者做Hp感染诊断,用放射免疫法检测TNF-α、IL-1β水平,免疫组织化学方法检测胃黏膜组织中iNOS表达.结果 248例慢性胃炎患者中,Hp阳性率为50.8%,Hp阴性率为49.2%;Hp阳性与阴性慢性胃炎患者胃黏膜炎症程度间差异有统计学意义(P＜0.01).Hp阳性组胃黏膜中TNF-α、IL-1β水平及iNOS阳性表达率分别为(1.32±0.21)ng/mg、(0.38±0.09)ng/mg和(68.74±5.78)%,Hp阴性组分别为(0.56±0.14)ng/mg、(0.11±0.02)ng/mg和(22.33±3.66)%,两组TNF-α、IL-1β的表达水平及iNOS阳性表达率间差异有统计学意义(P＜0.01).相关性分析表明,TNF-α、IL-1β及iNOS均与胃黏膜炎症程度、Hp感染呈正相关(P均＜0.05).结论 Hp相关性胃炎患者胃黏膜呈现一种炎症改变,这可能与细胞因子TNF-α、IL-1β、iNOS分泌增加有关.     

柔肝化纤颗粒对代偿期乙肝肝硬化肝肾阴虚型患者外周血NLRP3炎症小体及其产物表达的影响

目的   观察柔肝化纤颗粒对代偿期乙肝肝硬化肝肾阴虚型患者的临床疗效,及对血清核苷酸寡聚化结构域样受体蛋白3(NLRP3)炎症小体及其产物表达水平的影响。方法   80例患者随机分为治疗组、对照组各40例。2组按指南给予恩替卡韦口服,治疗组加服柔肝化纤颗粒。2组疗程均为24周。疗程结束后,比较2组肝功能、肝纤四项[Ⅲ型前胶原(PC-Ⅲ)、Ⅳ型胶原(Ⅳ-C)、层黏蛋白(LN)、透明质酸(HA)]、肝脾影像学指标、乙肝病毒(HBV)-DNA、中医证候积分、临床疗效、血清白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、肿瘤坏死因子-α(TNF-α)蛋白表达水平及NLRP3炎症小体、半胱氨酸天冬氨酸蛋白酶1(Caspase-1)、IL-1β、IL-18 mRNA的表达。结果   治疗后2组中医证候积分均较治疗前降低(P < 0.01), 治疗组优于对照组(P < 0.01);2组肝功能、肝纤四项、证候积分、肝脾影像学指标均优于治疗前(P < 0.01),且治疗组各项指标优于对照组(P < 0.01);2组血清IL-1β、IL-18、TNF-α水平均较治疗前下降,NLRP3、Caspase-1、IL-1β、IL-18 mRNA水平优于治疗前(P < 0.01),治疗组均较对照组作用显著(P < 0.01);治疗组总有效率高于对照组(P < 0.05)。结论   柔肝化纤颗粒联合恩替卡韦治疗代偿期乙肝肝硬化肝肾阴虚型患者临床疗效显著,其机制可能是通过抑制NLRP3炎症小体、Caspase-1、IL-1β、IL-18及TNF-α表达水平,有效抑制机体炎症反应,从而改善患者临床症状。