目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分...目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分为3组,第1组为退行性腰椎滑脱组(DLS)10例;第2组为腰椎间盘突出症组(LDH)17例,第3组为正常对照组10例,其中7例取自腰椎骨折手术病人,3例取自意外死亡者。应用EnV is ion二步免疫组化的方法检测其TGF-1β、BM P-2和typeⅡco llagen的表达情况,普通光镜观察,计算出各标本的表达阳性率和表达强度,数据以x-±s标准差及表达强度表示,结果分别用Spss统计软件和R id it进行分析。结果TGF-1β、BM P-2和typeⅡco llagen的阳性表达产物见于成纤维细胞、成软骨细胞和软骨细胞中,而Ⅱ型胶原染色还可同时见于基质。TGF-1β、BM P-2和typeⅡco llagen在DLS组中的表达明显高于LDH组和正常组(P<0.01或P<0.05),Ⅱ型胶原基质染色明显深于LDH组和对照组。LDH组的TGF-1β和typeⅡco llagen的表达阳性率和表达强度与正常组之间差异无显著性(P>0.05),而BM P-2的表达阳性率和表达强度在LDH组与正常组之间具有统计学意义(P<0.01)。结论黄韧带所受到的异常机械牵张力可以增加TGF-1β在黄韧带细胞中的合成,而TGF-1β则促进退行性腰椎滑脱黄韧带中的Ⅱ型胶原合成,导致黄韧带的退变和肥厚。BM P-2在退变黄韧带中的表达异常增高,可能与黄韧带的软骨化倾向有关。展开更多
AIM: To investigate the curative effects of oral and nasal administration of chicken type Ⅱ collagen (CⅡ) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions.METHODS: AA model in Sprague-Daw...AIM: To investigate the curative effects of oral and nasal administration of chicken type Ⅱ collagen (CⅡ) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions.METHODS: AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam, AA model+oral CⅡ, AA model+nasal CⅡ, AA model+meloxicam+oral C Ⅱ and AA model+meloxicam+nasal CⅡ(n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CⅡ intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis.RESULTS: Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CⅡ (20 μg/kg) could suppress the secondary hind paw swelling(P<0.05 for oral CⅡ; P<0.01 for nasal CⅡ), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes. However, oral administration of CⅡ (20 μg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and the curative effects of nasal CⅡ (20 μg/kg) were shown to be more efficient than that of oral CⅡ (20μg/kg) both in AA model and in AA+meloxicam model (P<0.05). CONCLUSION: Oral administration of CⅡ shows the limited efficacy on arthritis in AA rats with intestinal lesions, and nasal administration of CⅡ is more efficient than oral administration of CⅡ to induce mucosal tolerance in AA rats.展开更多
Objective: To explore the effect of radiofrequency hyperthermia on type Ⅱ collagen expression in a rabbit model of osteoarthri-tis (OA). Methods: Experimental model of knee OA was replicated in the right hind limbs o...Objective: To explore the effect of radiofrequency hyperthermia on type Ⅱ collagen expression in a rabbit model of osteoarthri-tis (OA). Methods: Experimental model of knee OA was replicated in the right hind limbs of 54 male rabbits by using modified Hulth modeling method. The rabbits were randomly divided into Model group, Lugua Polypeptide group and Radiofrequency Hyper-thermia group. After modeling, Lugua Polypeptide group was given intramuscular injection of Lugua polypeptide;Radiofre-quency Hyperthermia group was treated with radiofrequency hyperthermia;Model group was not given any special treatment. On the 7th, 13th and 19th day after radiofrequency hyperthermia, six experimental rabbits were chosen from each group and sacrificed to take out medial femoral condyle cartilages in the right hind limbs. Modified Mankins rating was applied to the morphological evaluation. Meanwhile, quantitative real-time PCR was used to detect the content of type Ⅱ collagen in cartilage tissues of medial femoral condyle. Results: At each time point after treatment, Mankins scores were decreased in all the 3 groups, with that of Model group sig-nificantly higher than those of the other two groups (Model group > Lugua Polypeptide group > Radiofrequency Hyperthermia group). The contents of type Ⅱ collagen in cartilage tissues were increased in all the 3 groups, with that of Radiofrequency Hyperthermia group significantly higher than those of the other two group (Model group < Lugua Polypeptide group < Ra-diofrequency Hyperthermia group). The difference between groups was of statistical significance (p < .05). For Radiofrequency Hyperthermia group, Mankins scores were decreased gradually as the treatment time went by, with the content of type Ⅱ colla-gen in cartilage tissues increased. The difference between time points was of statistical significance (p < .05). Conclusions: Radiofrequency hyperthermia is superior to Lugua polypeptide in the treatment of knee OA, at least in rabbits. Its therapeutic mechanism may be related to the significant increase in type Ⅱ collagen in cartilages.展开更多
AIM To evaluate the therapeutic effects of LLT on the type II collagen-induced arthritis in DBA/1 mice. LLT is a new compound derived from triptolide. LLT had been demonstrated in vitro and in vivo for its immunosuppr...AIM To evaluate the therapeutic effects of LLT on the type II collagen-induced arthritis in DBA/1 mice. LLT is a new compound derived from triptolide. LLT had been demonstrated in vitro and in vivo for its immunosuppressive activities, and our results showed LLT with low toxicity and high efficiency. LLTis a more drug-like compound comparing with the parent compound. METHODS Male DBA/1 mice were immunized at the tail base with 125 ( g of Bovine type II collagen emulsified in CFA containing Mycobacterium tuberculosis and boosted with collagen emulsified in IFA 3 weeks later. The severity of arthritis was graded visually and expressed using the arthritic index. The arthritic score of each mouse was obtained by scoring each limb as severity 0 to 4 and taken the sum of the scores of the four limbs.展开更多
The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T...The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T cells can be reduced through exposure to modified CⅡ(263-272)glycopeptide fragment via competitive inhibition with self-antigen.In this work,30 peptides based on the sequence of CⅡ(263-272)were prepared and evaluated for their binding to DR4 protein by surface plasmon resonance(SPR)assay.The effect on the secretion of pro-inflammatory factors by the spleen cells in collagen induced rheumatoid arthritis(CIA)mouse was also investigated.Two N-glycosylated CⅡ peptides were identified to have strong binding to the human recombinant DR4 protein and weak proinflammatory effect.These glycopeptides could be developed as therapeutic saccharide vaccines for the treatment of rheumatoid arthritis(RA).展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tri...To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant ( FCA) After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were obs erved in AA rats Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti collagen and anti Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN γ and TNF α i n articular steep in rats Results Oral administration of CⅡ was able to alleviate both distinctly articular and g eneral symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule The effects brought about by CⅡ were stron ger than those by Tripterygium Polyglycoside Oral administration of CⅡ inhibi ted antigen specific immune response, such as DTH and antibody reaction to CⅡ In addition, the expression of IFN γ and TNF α in joints were locally dow nregulated Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats Its remedial mechanisms are likely related to the downregulatio n of both IFN γ and TNF α, and the suppression of cell immunity展开更多
文摘目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分为3组,第1组为退行性腰椎滑脱组(DLS)10例;第2组为腰椎间盘突出症组(LDH)17例,第3组为正常对照组10例,其中7例取自腰椎骨折手术病人,3例取自意外死亡者。应用EnV is ion二步免疫组化的方法检测其TGF-1β、BM P-2和typeⅡco llagen的表达情况,普通光镜观察,计算出各标本的表达阳性率和表达强度,数据以x-±s标准差及表达强度表示,结果分别用Spss统计软件和R id it进行分析。结果TGF-1β、BM P-2和typeⅡco llagen的阳性表达产物见于成纤维细胞、成软骨细胞和软骨细胞中,而Ⅱ型胶原染色还可同时见于基质。TGF-1β、BM P-2和typeⅡco llagen在DLS组中的表达明显高于LDH组和正常组(P<0.01或P<0.05),Ⅱ型胶原基质染色明显深于LDH组和对照组。LDH组的TGF-1β和typeⅡco llagen的表达阳性率和表达强度与正常组之间差异无显著性(P>0.05),而BM P-2的表达阳性率和表达强度在LDH组与正常组之间具有统计学意义(P<0.01)。结论黄韧带所受到的异常机械牵张力可以增加TGF-1β在黄韧带细胞中的合成,而TGF-1β则促进退行性腰椎滑脱黄韧带中的Ⅱ型胶原合成,导致黄韧带的退变和肥厚。BM P-2在退变黄韧带中的表达异常增高,可能与黄韧带的软骨化倾向有关。
文摘AIM: To investigate the curative effects of oral and nasal administration of chicken type Ⅱ collagen (CⅡ) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions.METHODS: AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam, AA model+oral CⅡ, AA model+nasal CⅡ, AA model+meloxicam+oral C Ⅱ and AA model+meloxicam+nasal CⅡ(n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CⅡ intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis.RESULTS: Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CⅡ (20 μg/kg) could suppress the secondary hind paw swelling(P<0.05 for oral CⅡ; P<0.01 for nasal CⅡ), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes. However, oral administration of CⅡ (20 μg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and the curative effects of nasal CⅡ (20 μg/kg) were shown to be more efficient than that of oral CⅡ (20μg/kg) both in AA model and in AA+meloxicam model (P<0.05). CONCLUSION: Oral administration of CⅡ shows the limited efficacy on arthritis in AA rats with intestinal lesions, and nasal administration of CⅡ is more efficient than oral administration of CⅡ to induce mucosal tolerance in AA rats.
文摘Objective: To explore the effect of radiofrequency hyperthermia on type Ⅱ collagen expression in a rabbit model of osteoarthri-tis (OA). Methods: Experimental model of knee OA was replicated in the right hind limbs of 54 male rabbits by using modified Hulth modeling method. The rabbits were randomly divided into Model group, Lugua Polypeptide group and Radiofrequency Hyper-thermia group. After modeling, Lugua Polypeptide group was given intramuscular injection of Lugua polypeptide;Radiofre-quency Hyperthermia group was treated with radiofrequency hyperthermia;Model group was not given any special treatment. On the 7th, 13th and 19th day after radiofrequency hyperthermia, six experimental rabbits were chosen from each group and sacrificed to take out medial femoral condyle cartilages in the right hind limbs. Modified Mankins rating was applied to the morphological evaluation. Meanwhile, quantitative real-time PCR was used to detect the content of type Ⅱ collagen in cartilage tissues of medial femoral condyle. Results: At each time point after treatment, Mankins scores were decreased in all the 3 groups, with that of Model group sig-nificantly higher than those of the other two groups (Model group > Lugua Polypeptide group > Radiofrequency Hyperthermia group). The contents of type Ⅱ collagen in cartilage tissues were increased in all the 3 groups, with that of Radiofrequency Hyperthermia group significantly higher than those of the other two group (Model group < Lugua Polypeptide group < Ra-diofrequency Hyperthermia group). The difference between groups was of statistical significance (p < .05). For Radiofrequency Hyperthermia group, Mankins scores were decreased gradually as the treatment time went by, with the content of type Ⅱ colla-gen in cartilage tissues increased. The difference between time points was of statistical significance (p < .05). Conclusions: Radiofrequency hyperthermia is superior to Lugua polypeptide in the treatment of knee OA, at least in rabbits. Its therapeutic mechanism may be related to the significant increase in type Ⅱ collagen in cartilages.
文摘AIM To evaluate the therapeutic effects of LLT on the type II collagen-induced arthritis in DBA/1 mice. LLT is a new compound derived from triptolide. LLT had been demonstrated in vitro and in vivo for its immunosuppressive activities, and our results showed LLT with low toxicity and high efficiency. LLTis a more drug-like compound comparing with the parent compound. METHODS Male DBA/1 mice were immunized at the tail base with 125 ( g of Bovine type II collagen emulsified in CFA containing Mycobacterium tuberculosis and boosted with collagen emulsified in IFA 3 weeks later. The severity of arthritis was graded visually and expressed using the arthritic index. The arthritic score of each mouse was obtained by scoring each limb as severity 0 to 4 and taken the sum of the scores of the four limbs.
基金supported by the National Natural Science Foundation of China(Nos.81930097,21977005,82151223)supported by the National Key R&D Program of China(No.2022YFF1203005).
文摘The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T cells can be reduced through exposure to modified CⅡ(263-272)glycopeptide fragment via competitive inhibition with self-antigen.In this work,30 peptides based on the sequence of CⅡ(263-272)were prepared and evaluated for their binding to DR4 protein by surface plasmon resonance(SPR)assay.The effect on the secretion of pro-inflammatory factors by the spleen cells in collagen induced rheumatoid arthritis(CIA)mouse was also investigated.Two N-glycosylated CⅡ peptides were identified to have strong binding to the human recombinant DR4 protein and weak proinflammatory effect.These glycopeptides could be developed as therapeutic saccharide vaccines for the treatment of rheumatoid arthritis(RA).
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
文摘To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant ( FCA) After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were obs erved in AA rats Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti collagen and anti Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN γ and TNF α i n articular steep in rats Results Oral administration of CⅡ was able to alleviate both distinctly articular and g eneral symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule The effects brought about by CⅡ were stron ger than those by Tripterygium Polyglycoside Oral administration of CⅡ inhibi ted antigen specific immune response, such as DTH and antibody reaction to CⅡ In addition, the expression of IFN γ and TNF α in joints were locally dow nregulated Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats Its remedial mechanisms are likely related to the downregulatio n of both IFN γ and TNF α, and the suppression of cell immunity
