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1.
Age-related auditory pathology in the CBA/J mouse   总被引:10,自引:0,他引:10  
Commercially obtained aged male CBA/J mice presented a complex pattern of hearing loss and morphological changes. A significant threshold shift in auditory brainstem responses (ABR) occurred at 3 months of age at 4kHz without apparent loss of hair cells, rising slowly at later ages accompanied by loss of apical hair cells. A delayed high-frequency deficit started at 24kHz around the age of 12 months. At 20-26 months, threshold shifts at 12 and 24kHz and the accompanying hair cell loss at the base of the cochlea were highly variable with some animals appearing almost normal and others showing large deficits. Spiral ganglion cells degenerated by 18 months in all regions of the cochlea, with cell density reduced by approximately 25%. There was no degeneration of the stria vascularis and the endocochlear potential remained stable from 3 to 25 months of age regardless of whether the animals had normal or highly elevated ABR thresholds. The slow high-frequency hearing loss combined with a modest reduction of ganglion cell density and an unchanged endocochlear potential suggest sensorineural presbycusis. The superimposed early hearing loss at low frequencies, which is not seen in animals bred in-house, may complicate the use of these animals as a presbycusis model.  相似文献   

2.
OBJECTIVE: To describe a neglected anatomic variant occurring with presbycusis. STUDY DESIGN: Retrospective temporal bone histopathology study. METHODS: Quantitative analysis of peripheral hair cells, neurites, neurons, and the stria vascularis in temporal bones from individuals who had presbycusis. Fifty-three patients aged 65 years or older and with a down-sloping audiogram and clinical diagnosis of presbycusis were reviewed. Nine cases had normal hair and ganglion cell populations but reduced peripheral processes (neuritic presbycusis). These were compared with five normal-hearing controls on measurements of anterior middle and basal turn fiber bundle diameter and the ratio of basal to middle diameters. RESULTS: Thresholds at 4 and 8 kHz were significantly poorer in the neuritic presbycusis group than in the control group (p相似文献   

3.
Chen GD  Fechter LD 《Hearing research》2003,177(1-2):81-90
Noise-induced hearing loss (NIHL) and hair cell loss are known to show only a moderate correlation. One reason for this is that NIHL may reflect not only the sum of dead hair cells, but also the sum of impaired but still living hair cells. This report compares hair cell loss in different cochlear regions in rats with noise-induced compound action potential (CAP) threshold elevation at corresponding frequencies. CAP threshold elevation and hair cell loss were determined 4 weeks after noise exposure. In the apical turn (<35% from the apex) there was no hair cell loss even when a 60 dB CAP threshold elevation was induced. In the region of 40-60% from the apex in the middle turn, significant hair cell loss was not observed until CAP threshold elevation exceeded about 40-50 dB. This critical level decreased towards the basal turn. In the basal turn, outer hair cell (OHC) loss was observed in almost all of the noise-exposed rats, even in some cases without detectable NIHL, but inner hair cell (IHC) loss was still not observed until 50 dB threshold elevation. In the region of 75-90% from the apex related to the highest frequencies tested in this study (30-40 kHz), a linear NIHL/OHC loss relationship was observed. The results of this paper suggest that the high frequency hair cells in rat cochlea may die relatively rapidly after injury, leading to a linear relation between NIHL and hair cell loss, but that the low frequency hair cells may survive without auditory function.  相似文献   

4.
Influence of age on hair cell loss in the rabbit cochlea   总被引:1,自引:0,他引:1  
The surface preparation technique was used for a study of cochlear hair cell loss as a function of age in rabbits 1 week, 6 months, 1 year, and 4 years old. Cytocochleograms from these animals were prepared which indicated damaged or missing hair cells over the entire spiral organ from the apical to the basal coil. The loss in the mean percentage of total outer hair cells (OHC) and inner hair cells (IHC) appeared to increase linearly with increasing age, with a statistically significant correlation. The cell loss was similar in all three rows of OHC in each of the age groups. In animals up to 1 year of age, areas of OHC loss were localized in the apical and basal coils. In 4-year-old rabbits, OHC degeneration had become progressively accentuated and widespread. The pattern of IHC loss was somewhat similar to that of OHC. Age-related hair cell loss in the rabbit is comparable to that in the rat, monkey, and human cochlea.  相似文献   

5.
Cochleas from 16 Mongolian gerbils with spontaneous aural cholesteatomas, and four of similar age without cholesteatomas, were examined by scanning electron microscopy to quantify cochlear hair cell loss. Loss of hair cell stereocilia was found in all ears with cholesteatomas and was significantly increased when compared with uninvolved ears from animals of similar age. The hair cell loss associated with gerbilline cholesteatomas appeared to be most marked in the middle turn of the cochlea and increased in severity with increasing size of the cholesteatomas. Outer hair cells were affected more than inner hair cells. Inner and outer hair cell loss was not significantly different in infected cholesteatomas versus sterile cholesteatomas. The greater damage to hair cells at the middle turn compared to the basal turn suggests that these losses may be the result of some agent acting through the cochlear wall rather than through the round window.  相似文献   

6.
The purpose of this study was to investigate the effectiveness of 4-methylthiobenzoic acid (MTBA) as a protection agent against cisplatin (CDDP)-induced changes in organ of Corti surface structure, compared to electrophysiological changes. Electrophysiological change was assessed using auditory brainstem response (ABR) and morphological changes were assessed using scanning electron microscopy (SEM). Male Wistar rats underwent pre-treatment ABRs in response to clicks, and tone bursts at 2, 4, 8, 16, and 32 kHz. The three groups of rats were injected as follows: (1) MTBA (250 mg/kg, i.p.), (2) CDDP (16 mg/kg, i.p.), (3) CDDP+MTBA (16 mg/kg, i.p. + 250 mg/kg, i.p.). Post-treatment ABRs were performed 3 days after drug administration and rats were sacrificed. Their cochleae were harvested and SEM was used to examine the surface of the organ of Corti, specifically the number of inner hair cells (IHCs) and outer hair cells (OHCs) in the apical, middle and basal turns of the cochlea. Animal weight was measured on the first and final days. There was a good correlation between ABR threshold changes and hair cell loss in the high frequency region of the cochlea (basal turn), while threshold changes in the lower test frequencies (middle turn) appeared to be the result of more subtle changes in the cochlea. MTBA provided effective protection against cisplatin-induced ABR threshold changes at all test frequencies as well as hair cell loss. MTBA also protected against body weight loss.  相似文献   

7.

Objectives

The pathophysiology of tinnitus is obscure and its treatment is therefore elusive. Significant progress in this field can only be achieved by determining the mechanisms of tinnitus generation, and thus, histopathologic findings of the cochlea in presbycusis with tinnitus become crucial. We revealed the histopathologic findings of the cochlea in subjects with presbycusis and tinnitus.

Material and methods

The subjects were divided into 2 groups, presbycusis with tinnitus (tinnitus) group and presbycusis without tinnitus (control) group, with each group comprising 8 temporal bones from 8 subjects. We quantitatively analyzed the number of spiral ganglion cells, loss of cochlear inner and outer hair cells, and areas of the stria vascularis and spiral ligament.

Results

There was a significantly greater loss of outer hair cells in the tinnitus group compared with the control group in the basal and upper middle turns. The stria vascularis was more atrophic in the tinnitus group compared with the control group in the basal turn.

Conclusions

Tinnitus is more common in patients with presbycusis who have more severe degeneration of outer hair cells and stria vascularis.  相似文献   

8.
Chinchillas were exposed to octave band noise, sodium salicylate (300 mg/kg per day intraperitoneally), or the combination of both agents for 15 days. The octave band noise exposure was centered at 500 Hz at an intensity of either 80 or 105 dB sound pressure level. The effects of the experimental treatments were evaluated by determining the number of missing hair cells after recovery as a function of location within the cochlea using a surface preparation technique. Average cochleograms were calculated for each of five experimental groups. Animals given salicylate alone showed little or no hair cell loss. Noise exposure at 80 dB resulted in a mild (less than 30%) outer hair cell loss in the apical turn of the cochlea, whereas exposure at 105 dB resulted in moderate (50%) outer hair cell loss (outer hair cell first row particularly) in the apical half of the cochlea, mild outer hair cell loss in the basal region of the cochlea, and a mild loss of inner hair cells. The amount of hair cell loss in the groups exposed to the combination of salicylates and noise was not significantly different from the corresponding groups exposed to noise alone. Statistical analysis of the data suggest that the combination of salicylate plus noise does not produce any greater hair cell loss than noise alone.  相似文献   

9.

Objectives

Gentamicin (GM) is a commonly used aminoglycoside antibiotic that generates free oxygen radicals within the inner ear, which can cause vestibulo-cochlear toxicity and permanent damage to the sensory hair cells and neurons. Piper longum L. (PL) is a well-known spice and traditional medicine in Asia and Pacific islands, which has been reported to exhibit a wide spectrum of activity, including antioxidant activity. In this study, we evaluated the effect of hexane:ethanol (2:8) PL extract (subfraction of PL [SPL] extract) on GM-induced hair cell loss in basal, middle and apical regions in a neonatal cochlea cultures.

Methods

The protective effects of SPL extract were measured by phalloidin staining of cultures from postnatal day 2-3 mice with GM-induced hair cell loss. The anti-apoptosis activity of SPL extract was measured using double labeling by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and myosin-7a staining. The radical-scavenging activity of SPL extract was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay.

Results

SPL extract at a concentration of 1 µg/mL significantly inhibited GM-induced hair cell loss at basal and middle region of cochlea, while 5 µg/mL was effective against apical region hair cell loss. The protective effect of SPL extract was concentration dependent and hair cells retained their stereocilia in explants treated with SPL extract prior to treatment with 0.3 mM GM. SPL extract decreased GM-induced apoptosis of hair cells as assessed by TUNEL staining. The outer hair and inner hair counts were not decreased in SPL extract treated groups in compare to GM treated explants. Additionally, SPL extract showed concentration dependent radical scavenging activity in a DPPH assay.

Conclusion

An anti-apoptosis effect and potent radical scavenger activity of SPL extract protects from GM-induced hair cell loss at basal, middle and apical regions in neonatal cochlea cultures.  相似文献   

10.
目的观察体外培养的新生大鼠耳蜗Corti器经不同浓度硫酸新霉素处理后,各回毛细胞损伤情况。方法取新生大鼠完整耳蜗基底膜,体外培养12小时,存活贴壁后加药处理。对照组10个样本;3个实验组各10个样本,分别用终浓度为1mmol/L、2mmol/L、4mmol/L硫酸新霉素处理24小时。进行MyosinⅦa免疫荧光组织化学染色,在共聚焦显微镜下观察各回毛细胞缺失情况。分别选取10个图片进行毛细胞计数(每张图片截取100μm计数毛细胞个数),并利用CHISS软件进行统计分析。对照组除不加入硫酸新霉素外,其他培养条件均与实验组相同。结果硫酸新霉素对离体培养的新生大鼠耳蜗毛细胞具有损伤效应,且外毛细胞对硫酸新霉素的毒性作用比内毛细胞敏感。加入硫酸新霉素后,耳蜗毛细胞损失从底回外毛细胞开始,随着药物浓度增加,逐渐累及到中回,最后顶回受累,且损失程度随着浓度的递增而加重,以外毛细胞为甚。单纯体外培养的耳蜗毛细胞没有缺失。经完全随机设计方差分析可得:顶回正常组内毛细胞数量与新霉素1mmol/L组、2mmol/L组无统计学差异,与新霉素4mmol/L组有统计学差异;中、底回正常组内毛细胞数量与新霉素1mmol/L组、新霉素2mmol/L组、新霉素4mmol/L组均有统计学差异;顶回正常组外毛细胞数量与新霉素2mmol/L与4mmol/L组有统计学差异;中、底回正常组外毛细胞数量与新霉素1mmol/L组、新霉素2mmol/L组、新霉素4mmol/L组均有统计学差异。结论新生大鼠体外培养的耳蜗毛细胞随着硫酸新霉素药物浓度的增加损失越严重,且从底回向顶回发展,此与活体动物实验的损害规律基本相同,因此可作为耳毒性药物损伤后毛细胞再生研究的体外模型。  相似文献   

11.
Presbyacusis in humans is an age-related bilateral sensorineural hearing impairment generally associated with degeneration of cochlear hair cells and spiral ganglion cells (SGC) predominantly in the basal turn but present in the apical turn. Investigations of cochleas of aged rats and gerbils reveal a large loss of SGCs in the apical as well as the basal turns. Genetically inbred aged mice, on the other hand, seem to have variable amounts of SGC loss beginning in some strains very early in the life span of the animals and greatest in the basal turn.

Theee age groups of wild-caught, then laboratory-bred, mice were investigated to determine the pattern of SGC degeneration. In 18–19-month-old animals the main loss of SGCs occurred in the basal turn (49% loss compared to 2–3 months) followed by the apical turn (31%). The greatest SGC losses in the 28–31-month-old animals were in both the apical (76%) and basal turns (74%). Thus, this strain of mice is similar to other rodents in that both ends of the ganglion are affected by SGC degeneration associated with aging.  相似文献   


12.
目的 展示自然衰老和耳聋相关基因遗传缺陷之间耳蜗毛细胞缺失的不同模式。方法 用不同龄的长尾猴、南美栗鼠、豚鼠、Sprague-Dawley 大鼠、CBA/CaJ 小鼠、C57BL/6J 小鼠、A/J小鼠、DBA/2J 小鼠和侏儒灰色突变纯合子 (dwg/dwg) 小鼠作为受试对象。所有测试动物的耳蜗基底膜都被制作成平坦的耳蜗基底膜铺片。沿着耳蜗基底膜的全长,基底膜上所有的内外毛细胞都被完整计数,毛细胞的计数结果被输入到耳蜗图软件并自动生成每组实验条件的平均耳蜗图。结果 在天然衰老的动物中,耳蜗毛细胞的缺失总是发生在老年阶段。与此不同的是,在耳聋相关基因缺陷的动物中,耳蜗毛细胞的缺失却是发生在青年阶段甚至幼年阶段。发生在天然老化动物的耳蜗毛细胞缺失总是呈均匀分布或从耳蜗的顶回向底回扩展。 但是,发生在具有耳聋相关基因遗传缺陷动物的耳蜗毛细胞缺失却通常表现为从耳蜗的底回向顶回扩展。结论 本实验观察结果表明,发生在天然衰老的不具备耳聋相关基因缺陷动物身上的年龄相关性耳蜗毛细胞缺失反映的是真正由衰老引起的耳蜗退化性病变,而发生在伴有耳聋相关基因遗传缺陷的年幼动物身上的年龄相关性耳蜗毛细胞缺失可能与耳聋相关基因的遗传缺陷有关。  相似文献   

13.
Khanna SM  Hao LF 《Hearing research》2000,149(1-2):55-76
The apical turn of the anesthetized guinea pig cochlea was opened to examine the basilar membrane optically through the intact Reissner's membrane. Vibrations of the outer Hensen's cell and the basilar membrane (BM) adjacent to and about 130 microm below the level of the Hensen's cell were measured. Outer Hensen's cell vibration at the characteristic frequency was up to 900 times higher compared to the BM amplitude. After sacrifice BM vibration increased while Hensen's cell vibration decreased. The magnitude and sequence of change after sacrifice can best be explained by the presence of negative feedback between reticular lamina and BM. In other experiments using ototoxic drugs that damage outer hair cells, similar changes in Hensen's cell and BM vibration were observed. These results show that the apical turn behavior is different from that observed by other investigators in the basal turn. The potential benefits of the negative feedback are discussed. The presence of negative feedback would explain the linearity at the fundamental frequency observed in the apical turn of cochlea.  相似文献   

14.
Trimethyltin (TMT) is a potent ototoxicant which acutely disrupts generation of the action potential evoked by a broad range of tone frequencies and subsequently produces selective high frequency impairment and outer hair cell (OHC) damage in the extreme basal turn of the cochlea. We investigated the development of TMT ototoxicity in the guinea pig 6-48 h following treatment using the compound action potential (CAP), cochlear microphonic (CM), endocochlear potential (EP) and light and electron microscopic examinations. At all time intervals studied, TMT reduced CAP sensitivity and CM amplitude. The effect was relatively broad across test frequencies at 6 h and subsequently became restricted to higher frequencies. No disruption of the EP was observed between 6 and 24 h following TMT. OHC pathology in the basal turn of the cochlea 12 h following TMT consisted of vacuolization in the supranuclear region and disruption of the cuticular plate; some mitochondria exhibited dark inclusions. Type 1 spiral ganglion cells appeared swollen at 24 h with separation of myelin from the cell bodies. No pathological changes were observed in the inner hair cells (IHC). The present data identify the OHC as targets responsible for the loss of CM sensitivity after TMT as the EP was unaffected. These data suggest that CAP and CM recovery at low and middle frequencies following acute TMT administration is accompanied by recovery of neurotransmission at the IHC or Type 1 SGC level and OHC recovery at apical regions of the cochlea.  相似文献   

15.
全耳蜗毛细胞定量分析系统   总被引:1,自引:0,他引:1  
目的 介绍一种计算机辅助下的全耳蜗毛细胞定量分析系统。方法 选取氨基糖甙类药物损伤、噪声性损伤以及老年性聋动物模型的耳蜗制备全耳蜗基底膜铺片,从蜗尖向蜗底逐个视野依次进行内外毛细胞计数,将采集的数据输入到计算机并用毛细胞定量分析系统制备成耳蜗图。结果 氨基糖甙类药物耳蜗损害模型的耳蜗图显示毛细胞缺损自底回向顶回发展,外毛细胞的损伤比内毛细胞严重;强噪声引起的毛细胞破坏局限在与刺激声频率相对应的基底膜区域;6月龄C57BL/6J小鼠的耳蜗图显示老年性聋的早期损害起始于耳蜗底回的起始端,其中外毛细胞的破坏比内毛细胞严重。结论 耳蜗毛细胞定量分析系统可清晰显示全耳蜗毛细胞在基底膜上不同部位的损失程度和破坏范围,并可对应到基底膜上各个频率敏感部位。将传统的耳蜗铺片与计算机技术相结合制备的耳蜗图,具有全面可靠、简便精确、规范等优点。  相似文献   

16.
Data from systematic, light microscopic examination of cochlear histopathology in an age-graded series of C57BL/6 mice (1.5-15 months) were compared with threshold elevations (measured by auditory brain stem response) to elucidate the functionally important structural changes underlying age-related hearing loss in this inbred strain. In addition to quantifying the degree and extent of hair cell and neuronal loss, all structures of the cochlear duct were qualitatively evaluated and any degenerative changes were quantified. Hair cell and neuronal loss patterns suggested two degenerative processes. In the basal half of the cochlea, inner and outer hair cell loss proceeded from base to apex with increasing age, and loss of cochlear neurons was consistent with degeneration occurring secondary to inner hair cell loss. In the apical half of the cochlea with advancing age, there was selective loss of outer hair cells which increased from the middle to the extreme apex. A similar gradient of ganglion cell loss was noted, characterized by widespread somatic aggregation and demyelination. In addition to these changes in hair cells and their innervation, there was widespread degeneration of fibrocytes in the spiral ligament, especially among the type IV cell class. The cell loss in the ligament preceded the loss of hair cells and/or neurons in both space and time suggesting that fibrocyte pathology may be a primary cause of the hearing loss and ultimate sensory cell degeneration in this mouse strain.  相似文献   

17.
应用定量组织化学技术分析了CBA和C57BL小鼠耳蜗中糖元代谢的改变,发现18个月和36个月龄CBA小鼠的毛细胞和血管纹中,糖元含量比6周龄CBA正常小鼠明显增高,说明在自然老化CBA小鼠耳蜗中存在糖元储积现象。  相似文献   

18.
Ten puppy dogs (82, 131 or 148 days-old) from a Pointer cross-colony, exhibiting a juvenile severe hearing loss transmitted as an autosomal recessive trait, were used for histopathological characterization of the inner ear lesion. Immunostaining with calbindin, Na,K-ATPase, cytokeratins, S100, S100A1 and S100A6 antisera were helpful in identifying the different cell types in the degenerated cochleae.

Lesions, restricted to the Corti’s organ and spiral ganglion, were bilateral but sometimes slightly asymmetrical. Mild to severe lesions of the Corti’s organ were unevenly distributed among the different parts of the middle and basal cochlear turns while the apical turn remained unaffected at 148 days.

In 82 day-old puppies (n = 2), severe lesions of the Corti’s organ, meaning that it was replaced by a layer of unidentifiable cells, involved the lower middle and upper basal turns junction area, extending in the upper basal turn. Mild lesions of the Corti’s organ, with both hair and supporting cells abnormalities, involved the lower middle turn and extended from the rest of upper basal turn into the lower basal turn. The outer hair cells (ohc) were more affected than the inner hair cell (ihc). The lesions extended towards the basal end of the cochlea in the 131 (n = 5) and 148 (n = 3) day-old puppies. Additionally, the number of spiral ganglion neurons was reduced in the 131 and 148 day-old puppies; it is earlier than observed in most other canine hereditary deafness. These lesions were interpreted as a degeneration of the neuroepithelial type. This possible animal model might provide information about progressive juvenile hereditary deafness and neuronal retrograde degeneration investigations in human.  相似文献   


19.
Lesions of the hair cells in the cochlear apex were produced by a miniature cryoprobe and changes in behavioral auditory thresholds were measured. Monauralized adult chinchillas were behaviorally trained using operant procedures to produce pure-tone audiograms at frequencies from 63 Hz to 40 kHz. Following collection of baseline thresholds, the apical and middle turns of the experimental ear were visualized through a hole drilled in the bulla and a copper cryoprobe that had been cooled in liquid nitrogen was placed on the apical turn of the cochlea. Post-lesion threshold shifts from two subjects showed a flat loss of approximately 20 dB restricted to frequencies below either 710 Hz or 1 kHz; thresholds were normal at higher frequencies. The cytocochleograms, prepared from the ears following completion of threshold testing, show an almost complete loss of both inner and outer hair cells in the apical-most 20% of the cochlea with an abrupt transition region to areas of normal-looking hair cell populations. The relationship between the frequencies at which hearing was impaired and the location of missing hair cells along the basilar membrane is in agreement with the frequency-place map for the chinchilla of Eldredge et al. [(1981) J. Acoust. Soc. Am. 69, 1091-1095]. The magnitude of the loss, however, is less than might be expected based on comparison with threshold shifts produced by similar pathology in the basal turns.  相似文献   

20.
目的观察纯中药制剂对庆大霉素致聋动物和耳蜗毛细胞的修复再生作用。方法选用73只健康青年豚鼠,行听力学检查后,53只动物连续肌肉注射庆大霉素(80mg.kg-1.d-1)24~30天致聋(GM组),其间死亡8只,剩余45只随机分成中药治疗组(25只)和致聋后对照组(20只),中药治疗组给予纯中药制剂"复聪汤Ⅰ号"口服液和"复聪汤Ⅱ号"滴耳液治疗,致聋后对照组同法给予生理盐水。另外20只豚鼠作为正常对照组,每天肌肉注射等量生理盐水。在治疗30、60和90天后对GM组两组动物分别行ABR、DPOAE检测,同时,每一时间点处死6只动物,左侧耳蜗行扫描电镜观察,右侧耳蜗铺片行光镜观察和毛细胞计数。结果实验前所有豚鼠的听功能正常;连续注射庆大霉素30天后,GM组豚鼠ABR反应阈值上升到50~80dB SPL,DPOAE幅值降低,光镜和电镜下表现为耳蜗毛细胞纤毛断碎、倒伏、融合和消失,多处毛细胞表皮板肿胀、突起和疱疹样变性,或毛细胞被完全挤出网状板,基底回和第三回耳蜗毛细胞严重消失;中药治疗30天后,80%的耳聋豚鼠的ABR反应阈恢复到30~50dB SPL,DPOAE幅值明显提高;耳蜗铺片和电镜观察显示耳蜗毛细胞数目有一定恢复,组织结构有修复现象,扫描电镜可见再生毛细胞仅出现少量纤毛,而致聋后对照组未发现此种现象;治疗60天后,耳蜗毛细胞数目明显增多,Corti器的毛细胞区有大量的增殖细胞出现,扫描电镜可见成小束的新生纤毛出现在毛细胞缺失部位,同时支持细胞大量增殖;治疗90天后,再生的静纤毛束已基本形成,尤其是耳蜗基底部位的毛细胞明显增多,听功能基本正常。结论纯中药制剂复聪汤对庆大霉素致聋豚鼠耳蜗毛细胞有一定的修复和再生作用。  相似文献   

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