黄芩及Glucosamine/Chondroitin对类风湿性关节炎治疗作用的实验研究
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摘要
为了详细探讨黄芩(SB)和glucosamine/chondroitin(GC)及二者联合(联用后的药物以Arthrigia 命名)对类风湿性关节炎治疗作用的分子机制,选择RA 的体外模型-人关节滑膜细胞株MH7A 细胞和人软骨细胞株C28/I2 细胞,利用RT-PCR 及Western Blot 技术研究SB 和GC 对IL-1β和TNF-α细胞因子表达的影响,并检测SB 和GC 抗炎时对MMP-1 和MMP-13 mRNA 表达的影响。结果显示SB 可不同程度降低MH7A 细胞中MMP-1 和MMP-13 mRNA 的表达;GC 可轻微降低MH7A 细胞中MMP-1 mRNA 的表达;SB 可降低MH7A 细胞中TNF-α的蛋白表达,对IL-1β蛋白表达作用不明显。采用完全弗氏佐剂足跖部注射方式建立单侧后肢佐剂性关节炎的大鼠模型。对佐剂性关节炎的大鼠分别用SB、GC及不同浓度的Arthrigia 进行治疗给药,结果证实, Arthrigia 是一种有效的抗炎症及免疫调节性药物,可有效治疗或缓解类风湿性关节炎(RA)症状的出现。
本研究的结果揭示了黄芩和glucosamine/chondroitin在RA发病分子机制中的作用,为临床应用黄芩和glucosamine/chondroitin 治疗类风湿性关节炎以及新药Arthrigia 的开发提供试验依据。
Experimental Study on Therapeutic Effect of Scutellaria Baicalensis (SB)& Glucosamine/ Chondroitin (GC) on Rheumatoid Arthritis(RA).
Rheumatoid Arthritis(RA)is a systemic chronic autoimmune disease associated with progressive synovitis characterized by symmetry hyperplasia invading each joints in the body and resulting in the destruction of joint cartilage and capsule, and finally ankylosis. Besides joints, the other organs and tissues may be also involved. The prominent pathological changes are the infiltration of immunoreaction-related lymphocytes, plasmocytes and macrophages, as well as the formation of lymph follicles in joints and other organs or tissues involved. Being collagenosis, RA will lead to fibrinoid degeneration and necrosis of interstitial collagenous fibers. Although molecular biology, immunopathology and gene engineering technology have been used in the study on etiology and pathogeny of RA, the final definite conclusion is still not achieved. This leads to the difficulties in the clinical pharmacotherapy. At present, there are three groups of anti-RA drugs used in RA clinical therapy –NSAIDs, adrenocortical (ACH) and lentando drugs. With the effect of immunosuppression and anti-inflammatory, these drugs can restrain state of RA but can’t impede exacerbation. Additionally, many new drugs are in research and development, such as biological production, collagen type Ⅱand tetracyclines, but the therapeutic effects of these drugs still need further verification. There is still no such drug that is worldly
recognized for the control and treatment of RA. The effetive anti-RA drugs without toxic or side action are the object of pharmacologists, and also the hopes of patients. Scutellaria Baicalensis is a kind of Chinese herb with many pharmacological actions. Its main actions are antioxidation, anti-free radical, anti-inflammatory, anti-tumor, blocking calcium channel, inhibiting aldose reductase, anti-virus, anti-allergic reaction etc. Without any toxic or side roles, SB can protect immune, cardio-cerebral blood vessel, digestive and nerve system. Chondroitin is a kind of sulfated polysaccharide existing widely in cartilage, connective tissue, vascular wall, bladder, central neverse system, cornea and muscle tendon. Chondroitin helps maintaining soft and tenacity of joint, meanwhile, it promotes the repair of joint cartilage. Glucosamine is a kind of aminosugar in human or animal bodies. Being one of the most important nutrient in forming cartilage cells, Glucosamine distributs in cartilage and connective tissue as polysaccharide. It can promote the production of proteoglycan and collagen so as to supply articular fluid and essential substances in joint recovering after injury. Glucosamine is decomposed in amino acid which can transform into galactose and chondroitin. Moreover, glucosamine and chondroitin are all components without any toxicity of our body. Therefore, glucosamine/chondroitin has been used to relieve the discomfort of arthritis by the west for more than ten years. But there is no report on the combination therapy of SB and GC in RA treatment in the world. Our research is to study the RA therapeutic mechanism of GC and SB.
Based on it, further study the prevention and cure effect of the combination of SB and GC so as to develop an effective anti-RA drug without any toxic action. According to the common steps of new drugs development, we have done animal experiments and cell experiments respectively to study the anti-RA mechanism on integrate, cellular and molecular levels. In order to investigate the therapheutic effect on RA, we chose human synovial membrane (MH7A) and human cartilage cells (C28/I2), which were stimulated to produce the cellular RA models in vitro. We observed the effects of SA and GC on expression of IL-1β, TNF-α, MMP-1 and MMP-13 mRNA. The results showed that SA had no significant effect on the expression of IL-1βin MH7A and C28/I2 cells, but down-regulated the expression of TNF-α, suggesting that SA excerts its anti-RA by inhibition of TNF-α. SB down-regulated the expressions of MMP-1 mRNA and MMP-3 mRNA in normal and RA model cells dose dependently, suggesting that the mechanism of anti-RA of SB may be through the inhibition of the production and secretion of MMP-1 from synovial membrane cells. GC also down-regulated the expression of MMP-1 mRNA, suggesting that the anti-RA may be through the same mechanism as SB does. Besides the studies in vitro, we further examined the immunological mechanism of the combination of SB and glucosamine/chondroitin on anti-RA. With the adjuvant arthritis(AA) rat models, we observed the protective effects of oral SB, glucosamine/chondroitin and Arthrigia in different concentrations on AA in rats. Our research shows that 120mg/kgSB+10mg/kgGC has preventive role, whereas SB or GC alone has
本研究的结果揭示了黄芩和glucosamine/chondroitin在RA发病分子机制中的作用,为临床应用黄芩和glucosamine/chondroitin 治疗类风湿性关节炎以及新药Arthrigia 的开发提供试验依据。
Experimental Study on Therapeutic Effect of Scutellaria Baicalensis (SB)& Glucosamine/ Chondroitin (GC) on Rheumatoid Arthritis(RA).
Rheumatoid Arthritis(RA)is a systemic chronic autoimmune disease associated with progressive synovitis characterized by symmetry hyperplasia invading each joints in the body and resulting in the destruction of joint cartilage and capsule, and finally ankylosis. Besides joints, the other organs and tissues may be also involved. The prominent pathological changes are the infiltration of immunoreaction-related lymphocytes, plasmocytes and macrophages, as well as the formation of lymph follicles in joints and other organs or tissues involved. Being collagenosis, RA will lead to fibrinoid degeneration and necrosis of interstitial collagenous fibers. Although molecular biology, immunopathology and gene engineering technology have been used in the study on etiology and pathogeny of RA, the final definite conclusion is still not achieved. This leads to the difficulties in the clinical pharmacotherapy. At present, there are three groups of anti-RA drugs used in RA clinical therapy –NSAIDs, adrenocortical (ACH) and lentando drugs. With the effect of immunosuppression and anti-inflammatory, these drugs can restrain state of RA but can’t impede exacerbation. Additionally, many new drugs are in research and development, such as biological production, collagen type Ⅱand tetracyclines, but the therapeutic effects of these drugs still need further verification. There is still no such drug that is worldly
recognized for the control and treatment of RA. The effetive anti-RA drugs without toxic or side action are the object of pharmacologists, and also the hopes of patients. Scutellaria Baicalensis is a kind of Chinese herb with many pharmacological actions. Its main actions are antioxidation, anti-free radical, anti-inflammatory, anti-tumor, blocking calcium channel, inhibiting aldose reductase, anti-virus, anti-allergic reaction etc. Without any toxic or side roles, SB can protect immune, cardio-cerebral blood vessel, digestive and nerve system. Chondroitin is a kind of sulfated polysaccharide existing widely in cartilage, connective tissue, vascular wall, bladder, central neverse system, cornea and muscle tendon. Chondroitin helps maintaining soft and tenacity of joint, meanwhile, it promotes the repair of joint cartilage. Glucosamine is a kind of aminosugar in human or animal bodies. Being one of the most important nutrient in forming cartilage cells, Glucosamine distributs in cartilage and connective tissue as polysaccharide. It can promote the production of proteoglycan and collagen so as to supply articular fluid and essential substances in joint recovering after injury. Glucosamine is decomposed in amino acid which can transform into galactose and chondroitin. Moreover, glucosamine and chondroitin are all components without any toxicity of our body. Therefore, glucosamine/chondroitin has been used to relieve the discomfort of arthritis by the west for more than ten years. But there is no report on the combination therapy of SB and GC in RA treatment in the world. Our research is to study the RA therapeutic mechanism of GC and SB.
Based on it, further study the prevention and cure effect of the combination of SB and GC so as to develop an effective anti-RA drug without any toxic action. According to the common steps of new drugs development, we have done animal experiments and cell experiments respectively to study the anti-RA mechanism on integrate, cellular and molecular levels. In order to investigate the therapheutic effect on RA, we chose human synovial membrane (MH7A) and human cartilage cells (C28/I2), which were stimulated to produce the cellular RA models in vitro. We observed the effects of SA and GC on expression of IL-1β, TNF-α, MMP-1 and MMP-13 mRNA. The results showed that SA had no significant effect on the expression of IL-1βin MH7A and C28/I2 cells, but down-regulated the expression of TNF-α, suggesting that SA excerts its anti-RA by inhibition of TNF-α. SB down-regulated the expressions of MMP-1 mRNA and MMP-3 mRNA in normal and RA model cells dose dependently, suggesting that the mechanism of anti-RA of SB may be through the inhibition of the production and secretion of MMP-1 from synovial membrane cells. GC also down-regulated the expression of MMP-1 mRNA, suggesting that the anti-RA may be through the same mechanism as SB does. Besides the studies in vitro, we further examined the immunological mechanism of the combination of SB and glucosamine/chondroitin on anti-RA. With the adjuvant arthritis(AA) rat models, we observed the protective effects of oral SB, glucosamine/chondroitin and Arthrigia in different concentrations on AA in rats. Our research shows that 120mg/kgSB+10mg/kgGC has preventive role, whereas SB or GC alone has
引文
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