Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

超声小探头探查5、6级支气管路径对肺结节诊断的价值

目的 探讨超声小探头诊断5、6级支气管相关肺结节的影响因素。方法 收集2022年1月—2023年10月于临沂市人民医院薄层CT诊断肺外周结节的患者49例。薄层CT判断肺结节相关5级或6级支气管、测量结节的直径,评估实性结节、单纯磨玻璃结节。超声小探头测量5级管口到结节的距离、测量支气管相关结节的长度,判断超声小探头与结节的位置,统计分析以上因素对活检结果的影响。结果 49例患者活检阳性率79.59%,超声小探头测量结节的长度阳性组15.0(10.0,23.0)mm,阴性组11.0(2.0,20.8)mm(z=-11.220 P=0.022)。超声小探头在结节内部阳性率90.33%明显高于超声小探头在结节边缘的阳性率61.11%(χ^(2)=5.982,P=0.014)。CT测量结节的直径阳性组22.0(16.0,29.0)mm阴性组19.5(15.0,30.0)mm(z=-5.261,P=0.017)。性别、年龄、5级管口到结节的距离、实性结节、磨玻璃结节、5级支气管肺相关结节、6级支气管相关肺结节对活检阳性结果影响无统计学差异。结论 CT测量肺结节直径越大,超声小探头经5、6支气管测得肺结节长度越长,超声图像呈同心圆样改变,活检阳性率越高。

Cell viability and dopamine secretion of 6-hydroxydopamine-treated PC12 cells co-cultured with bone marrow-derived mesenchymal stem cells

In the present study, PC12 cells induced by 6-hydroxydopamine as a model of Parkinson＇s Disease, were used to investigate the protective effects of bone marrow-derived mesenchymal stem cells bone marrow-derived mesenchymal stem cells against 6-hydroxydopamine-induced neurotoxicity and to verify whether the mechanism of action relates to abnormal a-synuclein accumulation in cells Results showed that co-culture with bone marrow-derived mesenchymal stem cells enhanced PC12 cell viability and dopamine secretion in a cell dose-dependent manner. MitoLight staining was used to confirm that PC12 cells co-cultured with bone marrow-derived mesenchymal stem cells demonstrate reduced levels of cell apoptosis. Immunocytochemistry and western blot analysis found the quantity of α-synuclein accumulation was significantly reduced in PC12 cell and bone marrow-derived mesenchymal stem cell co-cultures. These results indicate that bone marrow-derived mesenchymal stem cells can attenuate 6-hydroxydopamine-induced cytotoxicity by reducing abnormal α-synuclein accumulation in PC12 cells.

Ghrelin alleviates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells

Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’s disease remain largely unexplored.The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine(6-OHDA)-induced Parkinson’s disease model and evaluate the potential underlying mechanisms.In the present study,we treated an SH-SY5 Y cell model with 6-OHDA,and observed that pretreatment with different concentrations of ghrelin(1,10,and 100 nM)for 30 minutes relieved the neurotoxic effects of 6-OHDA,as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide(PI)apoptosis assays.Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulatedα-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1(TGIF1),which was predicted as a potential transcription regulator of the gene encodingα-synuclein(SNCA).Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA.The Annexin V/PI apoptosis assay results revealed that inhibiting eitherα-synuclein or lincRNA-p21 expression with small interfering RNA(siRNA)relieved 6-OHDA-induced cell apoptosis.Furthermore,inhibiting lincRNA-p21 also partially upregulated TGIF1.By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays,we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1(STAU1)binding site and further activate the STAU1-mediated mRNA decay pathway.In addition,TGIF1 was able to transcriptionally regulateα-synuclein expression by binding to the promoter of SNCA.The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity.Collectively,these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.

Differences in brain pathological changes between rotenone and 6-hydroxydopamine Parkinson＇s disease models

Rotenone and 6-hydroxydopamine are two drugs commonly used to generate Parkinson＇s disease animal models.They not only achieve degenerative changes of dopaminergic neurons in the substantia nigra,but also satisfy the requirements for iron deposition.However,few studies have compared the characteristics of these two models by magnetic resonance imaging.In this study,rat models of Parkinson＇s disease were generated by injection of 3 μg rotenone or 10 μg 6-hydroxydopamine into the right substantia nigra.At 1,2,4,and 6 weeks after injection,coronal whole-brain T2-weighted imaging,transverse whole-brain T2-weighted imaging,and coronal diffusion tensor weighted imaging were conducted to measure fractional anisotropy and T2＊ values at the injury site.The fractional anisotropy value on the right side of the substantia nigra was remarkably lower at 6 weeks than at other time points in the rotenone group.In the 6-hydroxydopamine group,the fractional anisotropy value was decreased,but T2＊ values were increased on the right side of the substantia nigra at 1 week.Our findings confirm that the 6-hydroxydopamine-induced model is suitable for studying dopaminergic neurons over short periods,while the rotenone-induced model may be appropriate for studying the pathological and physiological processes of Parkinson＇s disease over long periods.

Detection of Human Papillomavirus DNA and E6/E7 mRNA from HPV Genotypes 16, 18, 31 and 33 in Histologically Confirmed Cases of Cervical Cancer and Precancerous Lesions in Burkina Faso

Introduction: Cervical cancer, caused by persistent high-risk human papillomavirus (HPV) infection, remains a global public health problem. The cellular transformation and maintenance of the malignant phenotype of these HPVs are attributed to the viral oncoproteins E6 and E7. Objective: This study aims to detect the presence of human papillomavirus DNA and E6/E7 oncoprotein mRNA of HPV genotypes 16, 18, 31 and 33 in cases of cervical cancer and precancerous lesions, histologically confirmed in Burkina Faso. Methods: This descriptive cross-sectional study focused on cases of cervical cancer and high-grade intraepithelial neoplasia (CIN) and was conducted from June to December 2022. One hundred (100) samples of fixed and paraffin-embedded tissues were collected from the pathological anatomy and cytology laboratories of hospitals in the capital of Burkina Faso. High-risk human papillomavirus (HR-HPV) DNA was detected using multiplex real-time PCR, while the presence of E6 and E7 mRNA in cervical cancer and high-grade CIN samples was determined using real-time Reverse Transcriptase-PCR (RT-PCR) with TaqMan probes. Results: The mean age of women diagnosed with cervical cancer and high-grade CIN was 50.81 ± 13.65 years, ranging from 22 to 82 years. Cervical cancer and high-grade CIN were positive for at least one high-risk human papillomavirus (HR-HPV) in 80% of cases. The most prevalent genotypes observed were HPV16, 18, 31, and 33, collectively accounting for 70.08% of cases. Of the 89 samples that tested positive for HR-HPV genotypes 16, 18, 31, and 33, 88 (98.88%;95% CI: [94.58 - 99.94]) were also positive for the presence of mRNA encoding the E6 and E7 oncoproteins of HPV16, 18, 31, and 33. Conclusion: In the presence of HPV DNA, testing for E6 and E7 oncoprotein mRNA could serve as a promising biomarker and valuable tool for improved assessment of the progression to cervical cancer.

胃癌患者病灶组织CK7、HER2、MLH1、MSH2及MSH6的表达变化研究

目的:探究胃癌患者病灶组织角蛋白7(CK7)、人表皮生长因子受体-2(HER2)、错配修复蛋白MutL同源物1(MLH1)、错配修复蛋白MutS同源物2(MSH2)及错配修复蛋白MutS同源物6(MSH6)的表达变化情况。方法:选取2020年2月—2023年1月苏州市相城人民医院收治的120例胃癌患者为研究对象,比较病灶组织及癌旁组织的CK7、HER2、MLH1、MSH2及MSH6的表达情况,并比较不同性别、年龄、TNM分期、分化程度、淋巴结转移情况及病灶位置者的病灶组织CK7、HER2、MLH1、MSH2及MSH6表达情况。结果:胃癌患者病灶组织CK7、HER2阳性率及MLH1、MSH2、MSH6表达缺失率显著高于癌旁组织,差异有统计学意义(P<0.05)。不同性别、年龄及病灶位置病灶组织的CK7、HER2、MLH1、MSH2及MSH6表达比较,差异无统计学意义(P>0.05);Ⅲ期、Ⅳ期病灶组织CK7、HER2阳性率高于Ⅰ期、Ⅱ期,MLH1、MSH2、MSH6表达缺失率均显著低于Ⅰ期、Ⅱ期,差异有统计学意义(P<0.05)。分化程度较低者病灶组织的CK7、HER2阳性率显著高于分化程度较高者,MLH1、MSH2及MSH6表达缺失率显著低于于分化程度较高者,差异有统计学意义(P<0.05)。有淋巴结转移者CK7、HER2阳性率显著高于无淋巴结转移者,MLH1、MSH2及MSH6表达缺失率显著低于无淋巴结转移者,差异有统计学意义(P<0.05)。结论:胃癌患者病灶组织的CK7、HER2、MLH1、MSH2及MSH6的表达相对异常,且不同TNM分期、分化程度及淋巴结转移情况者的差异较大。

基于CyclinD1-CDK4/6-P16通路探究欣胃颗粒对胃癌前病变大鼠细胞增殖的影响

目的基于CyclinD1-CDK4/6-P16通路探究欣胃颗粒对胃癌前病变大鼠细胞增殖的影响。方法将180只Wistar大鼠随机分为6组,每组30只:空白对照(空白)组、模型组、胃复春对照组、欣胃颗粒(低、中、高剂量)组,采用以MNNG法为主的复合造模方法制作PLGC大鼠模型。欣胃颗粒低、中、高剂量组分别以0.72 g·kg^(-1)、1.44 g·kg^(-1)、2.88 g·kg^(-1);胃复春组予0.52 g·kg^(-1),日一次灌胃给药,空白组与模型组给予同体量的生理盐水灌胃。实验周期为16周,结束后观察大鼠的一般情况,并用RT-PCR、Westernblotting技术检测胃黏膜中CyclinD1、CDK4/6、P16的mRNA及蛋白表达情况。结果欣胃颗粒各组和胃复春组大鼠的活动与饮食等情况同模型组相比都有不同程度的好转;与空白对照组相比,模型组CyclinD1、CDK4、CDK6的mRNA及蛋白表达水平显著升高;P16的mRNA及蛋白表达水平显著降低(P<0.05);欣胃颗粒(低、中、高剂量)组、胃复春组与模型组比较CyclinD1、CDK4、CDK6mRNA及蛋白表达水平均有降低;P16的mRNA及蛋白表达水平显著升高(P<0.05),其中欣胃颗粒中剂量组的疗效最为显著。结论欣胃颗粒通过CyclinD1-CDK4/6-P16通路参与细胞周期的调控,进而抑制PLGC细胞的增殖。

Dimethyl sulfide,a metabolite of the marine microorganism,protects SH-SY5Y cells against 6-hydroxydopamine and MPP~＋-induced apoptosis

Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.

Reduced glutathione alleviates the toxic effect of 6-hydroxydopamine on bone marrow stromal cells

We studied the effect of reduced glutathione on bone marrow stromal cells （BMSCs） treated with 6-hydroxydopamine （6-OHDA）, which shows a toxic effect on dopaminergic neurons. The proliferation of BMSCs treated with 6-OHDA decreased, while that of BMSCs treated with reduced glutathione increased. The proliferation of BMSCs treated with both 6-OHDA and reduced glutathione was significantly higher compared with that treated with 6-OHDA alone. These findings indicate that reduced glutathione alleviates the toxic effect of 6-OHDA on BMSCs.

核因子κB和白细胞介素-6在放射性膀胱损伤中的表达及意义

目的检测核因子κB(NF-κB)和白细胞介素-6(IL-6)在放射性膀胱损伤中的表达特征及其相关性。方法选择人输尿管上皮永生化细胞SV-HUC-1进行培养,分别应用5、10和15 Gy的X线照射24、48和72 h,将未行照射的SV-HUC-1细胞作为正常对照组。CCK-8检测细胞增殖活性,实时定量PCR检测NF-κB和IL-6 mRNA的表达。将siRNA-NF-κB质粒转染至15 Gy X线照射72 h后的细胞株建立siRNA-NF-κB组(si-NF-κB组),将未转染质粒的15 Gy X线照射72 h后细胞株作为空白对照组,Western blotting检测IL-6蛋白的表达。将20只雄性SD大鼠分为模型组(一次性给予20 Gy X线照射,建立放射性膀胱损伤大鼠模型)和对照组(不给予照射),每组10只,2周后处死大鼠,实时定量PCR检测膀胱组织中NF-κB和IL-6 mRNA的表达。结果SV-HUC-1细胞中,细胞增殖活性随着照射剂量和照射时间的增加而降低,NF-κB和IL-6 mRNA的表达随着照射剂量和照射时间的增加而增加。si-NF-κB组中IL-6的表达量明显低于空白对照组(P<0.05)。放射性膀胱损伤大鼠模型的膀胱病变组织中,NF-κB和IL-6 mRNA的表达明显高于对照组(P<0.05),NF-κB和IL-6 mRNA的表达呈正相关。结论X线对膀胱的损伤呈浓度和时间依赖性,病变组织中NF-κB和IL-6的表达升高,二者具有协同作用。

Protective Effect of Immaturue Bitter Orange(Citrus aurantium L.)Flavonoids Extracts on PC12 Cell Injury Induced by 6-Hydroxydopamine

To study the neuro protective effect of flavonoids extracts from immature bitter orange(Citrus aurantium L.),the PC12 cells treated with 6-hydroxydopamine(6-OHDA)were used as the Parkinson’s disease(PD)model.To determine the optimal dose of 6-OHDA for constructing a PD model,PC12 cells were incubated with different concentrations of 6-OHDA for 24 h.After 24 h incubation,PC12 cells of drug groups were added 6-OHDA and different concentrations of flavonoids extracts were measured cell viability by CCK8 for selecting effective concentration of flavonoids extracts;the ROS level was determined using flow cytometry;the levels of MDA,CAT,SOD and GSH-Px were assayed by Colorimetric kit for oxidative stress investigation.Compared with the model group,PC12 cell viability was significantly enhanced(P<0.05),the levels of ROS and MDA were reduced significantly(P<0.05),and the activities of SOD,CAT and GSH-Px were significantly enhanced(P<0.05)in drug groups.In conclusion,immature bitter orange flavonoids extracts could protect PC12 cells against 6-OHDA-induced oxidative stress.

Feasibility of establishing model of Parkinson disease by injecting 6-hydroxydopamine at different parts of the nigrostriatal pathway in the brain of rats

BACKGROUND： Previous researches found that animal models with Parkinson disease （PD） could be established by injecting 6-hydroxydopamine （6-OHDA） into medial forebrain bundle （MFB）, substantia nigra compacta （SNC） and caudate-putamen complex （CPU） of the nigrostriatal pathway. OBJECTIVE ： To compare behavioral, biochemica 6-OHDA injections in the areas of MFB, SNC and DESIGN： Controlled observational study and histological properties of these rats undergoing the CPU respectively. SEI-IING： Department of Neurology, First Affiliated Hospital of Guangxi Medical University MATERIALS： A total of 64 adult female SD rats weighing 180-230 g were provided by the Animal Experimental Center of Guangxi Medical University. 6-OHDA （Sigma Company, USA）; Brain solid positioner （Standard model 51600, Stoelting Co., IL, USA）; rotational monitoring of little animal （type QL-1, USA）; high liquid chromatography （HLC, Waters Company）. METHOOS： The experiment was carried out in the Medical Experimental Center of Guangxi Medical University from February to December 2005. ① According to digital table, 64 SD rats were divided into MFB group, SNC group, CPU group and control group with 16 in each group. On the basis of the brain atlas of Paxinos, rats in the first three groups were injected with 5 μL 6-OHDA into right MFB （0 mm of line of incisor tooth, A/P 4.4 mm, L/R 1.2 mm, ON -7.8 mm）, SNC （line of incisor tooth just equal to horizon, A/P -4.8 mm, L/R 1.6 mm, ON -7.8 mm） and CPU （0 mm of line of incisor tooth, A/P 1.2 mm, L/R 2.7 mm, ON -5.4 mm）, respectively. The rats in control group were injected with 5 μL ascorbic acid solution （2 g/L）. One week after operation, 0.1 g/L apomorphine （Apo, 0.05 mg/kg） was subcutaneously injected into neck and then rotational behavior induced by Apo was recorded once a week for 8 weeks. The PD models were considered successful only when rotational times more than or equal to 7 times per minute. Eight weeks after operation, micro-perfusion was used to obtain micro-perfusate in bilateral CPU and contents of 3,4-dihydroxyphenylacetic acid （3,4-DOPAC） and homovanillic acid （HVA） were also measured. In addition, amount of tyrosine hydroxylase positive cells （TH＊） in SNC was counted with immuno- histochemical staining. MAIN OUTCOME MEASURES ： ① Successful rate of PD models; ② contents of dopamine and its metabolite in MFB, SNC and CPU groups and TH＊ amount. RESULTS： All 64 SD rats were involved in the final analysis. ③ Successful rate and rotational behavior： One week after operation, there were 6 successful models both in SNC and MFB groups; in the 2^nd week, there were 6 both in SNC and MFB groups and 1 in CPU group; in the 3^nd week, there were 1 in MFB group and 3 in CPU group; in the 4^nd week, there were 3 in CPU group. Otherwise, no successful case was found out in the next 3 weeks. Abnormal rotational behavior was not observed in control group. Four weeks after operation, successful rates were 81% （13/16） in MFB group, 75% （12/16） in SNC group and 44% （7/16） in CPU group.② Contents of 3, 4-DOPAC and HVA： Eight weeks after operation, contents in the SNC area of the injured side were lower than those on non-lesion side （P 〈 0.01）.③Changes of TH＋ amount： Eight weeks after operation, TH＋ amount in the SNC area of the lesion side was lower than that on non-lesion side （P 〈 0.01 ）. CONCLUSION： Injecting 6-OHDA into MFB, SNC and CPU can damage dopaminergic cells and establish successful PD models.

高危型HPV阳性患者血清中HDAC6和Hsp90联合检测在宫颈癌前病变诊断中的临床意义

目的探究高危型人乳头瘤病毒(HR-HPV)阳性患者血清中组蛋白脱乙酰酶6(HDAC6)和热休克蛋白90(Hsp90)联合检测在宫颈癌前病变诊断中的临床意义。方法纳入2020年6月至2021年6月在山东第一医科大学附属济南妇幼保健院接受治疗的166例HR-HPV阳性患者作为研究对象,根据阴道镜检查和活检结果将研究对象分为实验组[高级别鳞状上皮内病变(HSIL)56例、低级别鳞状上皮内病变(LSIL)30例]、对照组(子宫颈良性病变患者80例)。采用酶联免疫吸附试验(ELISA)法检测患者血清HDAC6、Hsp90水平;采用Logistic多因素回归分析HR-HPV患者发生宫颈癌前病变的影响因素;采用受试者工作特征(ROC)曲线评价血清HDAC6、Hsp90对HR-HPV患者发生宫颈癌前病变的诊断价值。结果相较于对照组,实验组吸烟、有盆腔炎病史及性传播疾病感染史患者占比和白细胞、中性粒细胞、白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)、HDAC6、Hsp90水平显著升高(P<0.05)。Logistic多因素回归分析显示,性传播疾病感染史及IL-6、IL-1β、TNF-α、CRP、HDAC6、Hsp90水平均是HR-HPV阳性患者发生宫颈癌前病变的独立危险因素(P<0.05)。ROC曲线结果显示,血清HDAC6、Hsp90水平及二者联合预测HR-HPV阳性患者发生宫颈癌前病变的曲线下面积(AUC)分别为0.759、0.774、0.870,其中联合预测的AUC显著高于二者单独预测的AUC(Z=2.361、2.042,P<0.05)。HSIL患者IL-6、IL-1β、TNF-α、CRP、HDAC6、Hsp90水平显著高于LSIL患者(P<0.05)。结论血清HDAC6、Hsp90在HR-HPV阳性发生宫颈癌前病变患者中水平升高,均是HR-HPV阳性患者发生宫颈癌前病变的独立危险因素,有望成为HR-HPV阳性患者发生宫颈癌前病变的诊断因子。

基于文献数据库的6-OHDA帕金森病大鼠模型特点分析及在中药研究中的应用

目的分析6-OHDA诱导的大鼠PD模型的品系选择、性别、造模要素、模型评价方法以及在抗PD中药研究中的应用情况,以期为6-OHDA模型在帕金森研究中的应用提供参考。方法查阅近20年来中国知网(CNKI)和PubMed中应用6-OHDA建立PD大鼠模型的相关文献,分析6-OHDA诱导的大鼠PD模型的品系选择、性别体重、造模要素、模型评价方法以及在抗PD中药研究中的应用情况。结果6-OHDA诱导的大鼠PD模型多选用雄性SD或Wistar大鼠,造模时注射部位多为单侧黑质、内侧前脑束或纹状体,多在造模4周后检测阿扑吗啡诱导旋转实验、脑组织形态学、分子生物学、生化指标以判断模型成功率及防治PD药物的有效性。结论本文通过对6-OHDA诱导的大鼠PD模型的品系选择、性别、体重、造模要素、模型评价方法以及在抗PD中药研究中的应用情况进行分析,为PD模型的造模和应用提供参考。

IL-6、IL-10及相关炎症指标在川崎病冠状动脉损伤中的作用

目的探讨白介素-6(interleukin-6,IL-6)、白介素-10(interleukin-10,IL-10)以及相关炎症指标与川崎病(kawasaki disease,KD)的发生及其冠状动脉损伤的临床意义。方法选取2022年1—12月湖南省职业病防治院和湖南省人民医院40例川崎病住院患儿作为KD组,根据是否出现冠状动脉病变又划分为冠状动脉病变(coron aryartery lesions,CALs)组(n=9)与非冠状动脉病变(non-coron aryartery lesions,NCALs)组(n=31),选取40名健康体检者为健康对照组。抽取患儿发病的急性期以及健康对照组的外周静脉血,用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)测出IL-10、IL-6,同时收集C-反应蛋白(C-reactive protein,CRP)、血小板(platelet,PLT)、红细胞沉降率(erythrocyte sedimentation rate,ESR)、降钙素原(procalcitonin,PCT)指标。结果健康对照组和KD组急性期PCT、ESR、CRP、PLT、IL-10比较,差异有统计学意义(P<0.05)。CALs组与NCALs组的PLT及IL-10比较,差异有统计学意义(P<0.05)。Logistic回归分析显示,PLT为KD患儿发生冠状动脉病变的独立影响因素。结论PLT对于川崎病的发生及冠状动脉损伤的预测及判断有一定的临床价值。

Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

1,6-二磷酸果糖对大鼠缺血性心脑损伤的保护作用

目的 探讨口服 1,6 二磷酸果糖 (FDP)对大鼠缺血性心脑组织损伤的保护作用及其作用机制。方法 采用异丙肾上腺素 (Iso)致大鼠实验性心肌缺血模型。随机分为 3组 :对照组、Iso组 [5mg/(kg·d) ,7d]和Iso +FDP组 [Iso ,5mg/(kg·d) ,7d ;FDP ,6 g/(kg·d) ,2 1d],每组 8只。用光镜、电镜观察心、脑组织病理形态学改变。测定心肌肌浆网钙泵 (SERCA)活性、超氧化物歧化酶 (SOD)活性。结果 Iso组大鼠心肌组织病理可见大量纤维化病灶 ,病灶多呈片状、多灶性 ,还可见少许凝固坏死灶 ;亦可见脑组织病理损害、海马神经元密度较对照组降低。心肌SERCA活性 [0 .2 5 0± 0 .0 6 3μmol/(min·g·wetweight) ]较对照组 [0 .334± 0 .0 6 1μmol/(min·g·wetweight) ]降低。脑组织匀浆SOD活性 [2 3.2 2± 3.0 7U/(mg·pro) ]低于对照组 [4 4 .89± 2 .771U/(mg·pro) ]。FDP使心肌组织纤维化病灶减少 ,脑组织损害也明显减轻 ;FDP使心肌SERCA活性 [0 .312± 0 .0 6 7μmol/(min·g·wetweight) ]和SOD活性 [39.70± 3.4 4 1U/(mg·pro) ]增高。结论 口服FDP可减轻大鼠心肌和脑组织病理改变 。

重症颅脑损伤后TNF-α及IL-6在急性心肌功能损害中的作用

目的探讨肿瘤坏死因子-α(TNF-α)、IL-6在重症颅脑损伤后心肌功能损害发生过程中的作用。方法以2009年2月至2012年5月在该院急诊科就诊,符合重症颅脑损伤的诊断标准,格拉斯哥昏迷评分(GCS)≤8分,除外合并其他部位损伤及在急诊科内死亡的患者为观察对象,共65例,在抢救治疗的同时抽血化验肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白T(cTnT)、TNF-α、IL-6,检验结果与对照组进行比较,并对观察组病例的检验结果进行相关性分析。结果观察组心肌功能检验结果:CKMB(198.63±37.72)U/L,cTnT(548.17±49.58)pg/mL;损伤因子检验结果:TNF-α(39.93±18.88)ng/mL,IL-6(469.61±73.66)ng/mL,与对照组同类数据比较,差异有统计学意义(P<0.01)。观察组CK-MB与TNF-α、IL-6比较,其r>0.911 4;cTnT与TNF-α、IL-6比较,r>0.942 1,差异均有统计学意义(P<0.01),呈显著正相关。结论 TNF-α和IL-6参与了重症颅脑损伤后急性心肌功能损害的发生、发展过程,抑制它们在血液中的高浓度表达,或有可能减轻颅脑损伤后心肌功能损害的程度。

RV肠炎伴肠外脏器损害患儿血清PCT、IL-6、TNF-α水平变化及意义

目的观察急性轮状病毒(RV)肠炎伴肠外脏器损害患儿血清降钙素原(PCT)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的水平变化,并探讨其意义。方法根据肠外脏器损害的情况将117例RV肠炎患儿分为肝脏损害组(21例)、心脏损害组(16例)、呼吸系统损害组(15例)、中枢神经系统损害组(12例)、多脏器损害组(20例)及无肠外脏器损害组(33例),检测各组患儿血清PCT、IL-6、TNF-α水平。结果多脏器损害组血清PCT水平高于其他单脏器损害组,肝脏损害组、心脏损害组、多脏器损害组血清PCT水平高于无肠外脏器损害组(P均<0.01)。肝脏损害组、心脏损害组、中枢神经系统损害组、多脏器损害组血清IL-6水平高于无肠外脏器损害组(P均<0.01)。肝脏损害组、心脏损害组、多脏器损害组血清TNF-α水平高于无肠外脏器损害组(P均<0.01)。结论 RV肠炎伴肠外脏器损害患儿血清PCT、IL-6、TNF-α水平增高,三者与肠外脏器损害的发生有关,共同参与了RV肠炎的发生发展。