云南白药对实验性类风湿关节炎与牙周炎相关性干预研究
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摘要
【目的】探讨牙周炎与类风湿关节炎的相关性以及云南白药控制炎症减少骨破坏的机制。
【方法】选用7～8周龄健康雄性SD大鼠128只,称重后随机分为四组：正常组(32只),单纯模型组(32只),模型+云南白药组(32只),模型+甲氨蝶呤组(32只)。造模组每只大鼠在尾根部多点注射0.2ml以及在左后足跖垫注射0.1ml的胶原乳剂,第一次注射后7天及21天再次尾根部注射0.2ml加强免疫。云南白药组和甲氨蝶呤组都于第一次加强免疫同时采用灌胃法给药。分别于给药后1W,2W,3W,4W每组取八只,乙醚麻醉心脏采血后处死,处死后取上颌骨及肿胀较明显后肢,用于后期形态学,组织学及血清学的检测。观察指标包括：(1)：大鼠的体重、足爪厚度、关节炎评分。(2)：组织学指标：HE染色观测牙槽骨及牙龈组织变化和关节中炎性细胞浸润情况。TRAP染色观察关节骨的破骨细胞以确定模型的成功。碱性磷酸酶及RANKL免疫组化染色观察牙槽骨中阳性表达细胞的变化。(3)：血清学指标：ELISA方法检测血清中IL-1β、PGE2水平的变化。各组间数据比较采用多个样本均数的两两比较。
【结果】云南白药组和甲氨蝶呤组,随着给药时间的延长关节组织炎症反应逐渐减轻,并明显抑制了外周血IL-1β、PGE2的表达(表6-7)。给药2W起,足爪肿胀度、关节炎评分、滑膜炎症侵润均明显轻于模型组(表2-3)。体重仅在第12天增长没有正常组明显(表1)。第4W仅模型组关节组织中观察到了阳性破骨细胞。与模型组相比,给药1W后,云南白药组和甲氨蝶呤组均明显降低了牙槽骨中RANKL阳性表达的光密度值(表4),给药3W后,增加了牙槽骨中碱性磷酸酶阳性表达面积,并且云南白药组效果优于甲氨蝶呤组(表5)。
【结论】大鼠实验性类风湿关节炎时可引起牙槽骨中破骨细胞活化因子(RANKL)表达的上调,并代偿性促成骨活性因子(ALP)的表达。云南白药及甲氨蝶呤可下调破骨细胞活化因子表达,促进成骨活性因子的表达。同时,云南白药类似甲氨蝶呤可降低了关节肿胀度,抑制了关节炎症的发展,降低外周血血浆中IL-1β,PGE2的水平。
Objective:The purpose of this study was to discuss the relationship between periodontitis and rheumatoid arthritis, the mechanism of Yunnan Baiyao controlling inflammation and decreasing bone damage
Methods:128 male SD rats,7～8 week-old, were randomly divided into four groups: normal group (N,32rats), simple model group (SM,32rats), model with Yunnan Baiyao (YM,32rats), model with methotrexate group (MM,32rats). each rat,except normal group,were injected 0.2ml collagen emulsions in tail root and 0.1ml collagen emulsions in the metatarsal mat of the left foot, on the day of 7 th and 21th after the first injection,reinjected 0.2 ml collagen emulsions to each rat. On the day of 7 th,did the gastric perfusion with Yunnan Baiyao and methotrexate to each rat of model with Yunnan Baiyao and metatarsal. On the week of 1th、2th、3th、4th,blood sample was taked from heart under anesthesia and tissues were collected from each group.Observe indicators include:(1):rat weight, foot claw thickness, arthritis score. (2):histologic index:HE staining was emplayed to observe the changes of alveolar and gum tissue and infiltrating joints of inflammatory cells.The TRAP staining was emplayed to observe the osteoclast in joint. With Alkaline phosphatase and RANKL immunohistochemical staining to study positive changes of express cell in alveolar bone. (3):serological index: ELISA was used to detect the level of the IL-1beta, PGE2 in serum.Statistical analysis were performed with pairwise comparison of the differences sample mean.
Results:The joint inflammatory response in group YM and group MM was reduced along with the extension of time of medication administration, the level of IL-1 beta, PGE2 expression was significantly inhibited(Table6-7). Form the second week with the medication,the inflammation response was less in group YM and group MM compared with group SM(Table2-3). Weight growth,in the first 12 days, were lighter than normal group (Table 1).positive osteoclas were only obsered in group SM in 4w. Compared with group SM after did medicine 1 w, the express of RANKL positive in alveolar bone obviously decrease in group YM and group MM(Table4), alkaline phosphatase positive express area had increased in group YM and group MM after 3w with medications(Table5).
Conclusion:Rat experimental rheumatoid arthritis can potentially raise the express of activator of the osteoclast(RANKL), compensately promote bone active factor (ALP) expression. Yunnanbaiyao and methotrexate can restrain the expression of the osteoclast active factor, promote osteogenesis active factor expression. Meanwhile, Yunnan Baiyao, like methotrexate, can reduce the joint swelling degree, inhibit the development of the joint inflammation, reduce the level of PGE2 and IL-lbeta in the peripheral blood plasma.
【方法】选用7～8周龄健康雄性SD大鼠128只,称重后随机分为四组：正常组(32只),单纯模型组(32只),模型+云南白药组(32只),模型+甲氨蝶呤组(32只)。造模组每只大鼠在尾根部多点注射0.2ml以及在左后足跖垫注射0.1ml的胶原乳剂,第一次注射后7天及21天再次尾根部注射0.2ml加强免疫。云南白药组和甲氨蝶呤组都于第一次加强免疫同时采用灌胃法给药。分别于给药后1W,2W,3W,4W每组取八只,乙醚麻醉心脏采血后处死,处死后取上颌骨及肿胀较明显后肢,用于后期形态学,组织学及血清学的检测。观察指标包括：(1)：大鼠的体重、足爪厚度、关节炎评分。(2)：组织学指标：HE染色观测牙槽骨及牙龈组织变化和关节中炎性细胞浸润情况。TRAP染色观察关节骨的破骨细胞以确定模型的成功。碱性磷酸酶及RANKL免疫组化染色观察牙槽骨中阳性表达细胞的变化。(3)：血清学指标：ELISA方法检测血清中IL-1β、PGE2水平的变化。各组间数据比较采用多个样本均数的两两比较。
【结果】云南白药组和甲氨蝶呤组,随着给药时间的延长关节组织炎症反应逐渐减轻,并明显抑制了外周血IL-1β、PGE2的表达(表6-7)。给药2W起,足爪肿胀度、关节炎评分、滑膜炎症侵润均明显轻于模型组(表2-3)。体重仅在第12天增长没有正常组明显(表1)。第4W仅模型组关节组织中观察到了阳性破骨细胞。与模型组相比,给药1W后,云南白药组和甲氨蝶呤组均明显降低了牙槽骨中RANKL阳性表达的光密度值(表4),给药3W后,增加了牙槽骨中碱性磷酸酶阳性表达面积,并且云南白药组效果优于甲氨蝶呤组(表5)。
【结论】大鼠实验性类风湿关节炎时可引起牙槽骨中破骨细胞活化因子(RANKL)表达的上调,并代偿性促成骨活性因子(ALP)的表达。云南白药及甲氨蝶呤可下调破骨细胞活化因子表达,促进成骨活性因子的表达。同时,云南白药类似甲氨蝶呤可降低了关节肿胀度,抑制了关节炎症的发展,降低外周血血浆中IL-1β,PGE2的水平。
Objective:The purpose of this study was to discuss the relationship between periodontitis and rheumatoid arthritis, the mechanism of Yunnan Baiyao controlling inflammation and decreasing bone damage
Methods:128 male SD rats,7～8 week-old, were randomly divided into four groups: normal group (N,32rats), simple model group (SM,32rats), model with Yunnan Baiyao (YM,32rats), model with methotrexate group (MM,32rats). each rat,except normal group,were injected 0.2ml collagen emulsions in tail root and 0.1ml collagen emulsions in the metatarsal mat of the left foot, on the day of 7 th and 21th after the first injection,reinjected 0.2 ml collagen emulsions to each rat. On the day of 7 th,did the gastric perfusion with Yunnan Baiyao and methotrexate to each rat of model with Yunnan Baiyao and metatarsal. On the week of 1th、2th、3th、4th,blood sample was taked from heart under anesthesia and tissues were collected from each group.Observe indicators include:(1):rat weight, foot claw thickness, arthritis score. (2):histologic index:HE staining was emplayed to observe the changes of alveolar and gum tissue and infiltrating joints of inflammatory cells.The TRAP staining was emplayed to observe the osteoclast in joint. With Alkaline phosphatase and RANKL immunohistochemical staining to study positive changes of express cell in alveolar bone. (3):serological index: ELISA was used to detect the level of the IL-1beta, PGE2 in serum.Statistical analysis were performed with pairwise comparison of the differences sample mean.
Results:The joint inflammatory response in group YM and group MM was reduced along with the extension of time of medication administration, the level of IL-1 beta, PGE2 expression was significantly inhibited(Table6-7). Form the second week with the medication,the inflammation response was less in group YM and group MM compared with group SM(Table2-3). Weight growth,in the first 12 days, were lighter than normal group (Table 1).positive osteoclas were only obsered in group SM in 4w. Compared with group SM after did medicine 1 w, the express of RANKL positive in alveolar bone obviously decrease in group YM and group MM(Table4), alkaline phosphatase positive express area had increased in group YM and group MM after 3w with medications(Table5).
Conclusion:Rat experimental rheumatoid arthritis can potentially raise the express of activator of the osteoclast(RANKL), compensately promote bone active factor (ALP) expression. Yunnanbaiyao and methotrexate can restrain the expression of the osteoclast active factor, promote osteogenesis active factor expression. Meanwhile, Yunnan Baiyao, like methotrexate, can reduce the joint swelling degree, inhibit the development of the joint inflammation, reduce the level of PGE2 and IL-lbeta in the peripheral blood plasma.
引文
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