醇提红曲对去势骨质疏松模型大鼠的影响及其作用机制的探讨
摘要
目的:初步探讨醇提红曲对去势大鼠BMD、体重及OPG、ALP的影响及其防治骨质疏松的机理。
方法一:根据现代药理研究结果,利用乙醇溶解、超声波振荡、水浴氮气条件下蒸去乙醇来提取红曲的有效成分。
结果一:采用乙醇溶解、超声波振荡、在水浴氮气条件下使用旋转蒸发器的方法可以充分溶解红曲粉末,有效浓缩红曲醇提液。
方法二:采用去势骨质疏松的动物模型,以鲑鱼降钙素作为阳性对照,采用重复测量设计分析红曲对大鼠BMD、体重的影响。将6月龄雌性Wister大鼠32只随机分为四组,每组8只:假手术组(A组)、红曲组(B组)、降钙素组(C组)、模型组(D组);假手术组不摘除卵巢、切除卵巢周围少量脂肪组,余组切除双侧卵巢;术后1周开始药物干预,于1周末、6周末、12周末测量大鼠左侧股骨骨密度及体重;12周末处死动物,采用ELISA和紫外可见分光光度法分别观测大鼠OPG、ALP的表达,评价醇提红曲对去势大鼠的治疗效果。
结果二:1.骨密度:①不同干预因素各组间差异有统计学意义F=3.85 P=0.0199;测定时间之间的差异具有显著的统计学意义F=776.79 P＜0.0001;②多重比较:1周末、6周末四组总体均数无明显差异;12周末四组总体均数有明显差异:A组与B组、C组、D组的总体均数有差异,B组与A组、C组、D组的总体均数有差异,C组与A组、B组、D组的总体均数有差异,D组与A组、B组、C组的总体均数有差异。
2.体重:①不同干预因素各组间差异有统计学意义F=5.55 P=0.0041;测定时间之间的差异具有显著的统计学意义F=254.53 P＜0.0001;②多重比较:1周末、6周末四组总体均数无差异;12周末四组总体均数有差异,A组与B组、C组、D组的总体均数有差异,B组与A组的总体均数有差异,C组与A组的总体均数有差异,D组与A组的总体均数有差异,还不能认为B组、C组与D组的总体均数有差异。
3.OPG:各组间OPG总体均数有统计学差异F=5.29 P=0.0051;多重比较:说明A组与B组、C组、D组的OPG总体均数有差异,B组与A组、C组、D组的OPG总体均数有差异,C组与A组、B组、D组的OPG总体均数有差异,D组与A组、B组、C组的OPG总体均数有差异。
4.ALP:各组间ALP总体均数有统计学差异F=12.14 P＜0.0001;多重比较:说明A组与B组、D组的ALP总体均数有差异,B组与A组、C组、D组的ALP总体均数有差异,C组与B组、D组的ALP总体均数有差异,D组与A组、B组、C组的ALP总体均数有差异,还不能认为A组与C组的ALP总体均数有差异。
5.BMD值和OPG含量直线相关分析相关分析有统计学差异r=0.38167P=0.0311,BMD值和OPG含量之间存在正的直线相关关系。
6.OPG和ALP直线相关分析相关分析有统计学差异r=-0.10034 P=0.5848,OPG含量和ALP含量之间无直线相关关系。
7.BMD值和ALP含量直线相关分析相关分析有统计学差异r=-0.66048P＜0.0001,BMD值和ALP含量之间存在负的直线相关关系。
8.骨切片形态学观察:模型组股骨骨小梁大片消失,髓腔内残留纽扣样或棒状骨小梁结构,骨小梁连接断裂,排列疏松;假手术组股骨骨小梁结构呈网孔状,连接紧密,排列规则,骨小梁壁厚度一致。
结论:1.采用乙醇溶解、超声波振荡、在水浴氮气条件下使用旋转蒸发器的方法可以充分溶解红曲粉末,有效浓缩红曲醇提液。
2.模型组骨密度明显低于假手术组,股骨骨小梁大片消失,血清ALP含量明显高于假手术组,动物模型表现为骨量降低、骨微结构破坏、骨代谢高转换率,表明动物模型较为可靠。
3.实验结果证实红曲对去势大鼠骨密度值有一定的提高作用,可以有效降低去势大鼠的骨转换率、减缓由于雌激素分泌减少而造成的骨量减少,可用于绝经后骨质疏松的预防和治疗;BMD值与血清OPG含量存在正相关关系,说明大鼠骨密度下降与血清OPG含量降低有关;推测红曲其作用可能是通过改变血清OPG含量来实现的。
Objective:To explore the effects of Monascus on bone mineral density,weight,OPG and ALP in ovariectomized rats.To investigate the theraputic effects and mechanicms of Monascus in postmenop- ausal osteoporosis.
Methods1:According to modern pharmacological research findings,the use of ethanol solution, ultrasonic vibration,Bath nitrogen conditions to ethanol distilled to extract Monascus the active ingredients
Result1:Ethanol solution,ultrasonic vibration,Nitrogen in water bath for use rotary evaporator method can be fully dissolved Monascus powder,effective Concentration Monascus alcohol extract.
Methods2:Monascus was exaracted using dissolution of alcohol and vibration of ultrasound.Thirty- two female rats were rangomly divideded into four groups,8 in each:shame group-A group,Monascus group-B group,salmon calcitionin group-c group and ovariectomy group-d group.Bone mineral densities and weights of each group were measured at 1 week,6 week and 12 week after operation.The rats were killed at 12 week.OPG and ALP were measured by enzyme-linked immunosorbent assay and ulcraviolet-visible spectrophotometry.
Result2:1.BMD:①different factors of the intervention group are significantly different F=3.85 P=0.0199;Determination of the time difference was significant statistically significant F=776.79 P＜0.0001;②multiple comparisons:four groups in one weekend and six weekend overall mean no significant difference;In12 weekend there are significant differences:Group A is different from GroupB,GroupC and GroupD;Group B is different from Group A,Group C and GroupD;Group C is different from GroupA GroupB and GroupD;Group D is different from GroupA,GroupB and GroupC;
2.Weight:①different factors of the intervention group are significantly different F=5.55 P=0.0041;Determination of the time difference is significant statistically significant F=254.53 P＜0.0001;②multiple comparisons:Group A is different from GroupB GroupC GroupD;Group B is different from GroupA;Group C is different from GroupA;Group D is different from GroupA;there is no different among GroupB GroupC GroupD.
3.OPG:There is different between in four groups F=5.29 P=0.0051;multiple comparison:Group A is different from GroupB GroupC GroupD;Group B is different from GroupA GroupC GroupD;Group C is different from GroupA GroupB GroupD;Group D is different from GroupA GroupB GroupC;
4.ALP:There is different between in four groups F=12.14 P＜0.0001;multiple comp -arison:Group A is different from GroupB and GroupD;Group B is different from GroupA Group Cand GroupD;Group C is different from GroupB and GroupD;Group D is different from GroupA,GroupB and GroupC;
5.OPG and BMD of linear correlation analysis was statistically relevant difference r=0.38167 P=0.0311,there is a positive linear relationship between OPG and BMD.
6.OPG and ALPof linear correlation analysis was statistically different r=-0.10034 P=0.5848,there is no linear relationship between OPG and ALP.
7.BMD and ALP of linear correlation analysis was statistically relevant difference r=-0.66048 P＜0.0001,there is a negative linear relationship between BMD and ALP.
8.Bone biopsy morphology:the model group femurs large disappeared marrow remnant button or rod-like trabecular bone structure,trabecular bone connecting fracture,with osteoporosis;sham group femoral trabecular bone structure showed mesh-like connecting closely with the rules,trabecular thickness consistency.
Conclusion:1.Ethanol solution,ultrasonic vibration,Nitrogen in water bath for use rotary evaporator method can be fully dissolved Monascus powder,effective concentration Monascus alcohol extract.
2.BMD of model was lower than that of sham-operated group,femurs large disappear,serum ALP was significantly higher than that of the sham-operated group,animal model showed reduced bone mass and bone-destroying the structure,bone metabolism high conversion rate,animal models indicate more reliable.
3.The experimental results confirmed Monascus on BMD in ovariectomized rats with an increase,can effectively reduce the ovariectomized rat bone turnover rate,Slowed down due to reduced estrogen secretion caused by bone loss.Monascus can be used for postmenopausal osteoporosis prevention and treatment;s there is a positive correlation between the BMD and serum OPG level,There is a relationship between decreasement of rats bone mineral density and lowerment serum OPG levels.
方法一:根据现代药理研究结果,利用乙醇溶解、超声波振荡、水浴氮气条件下蒸去乙醇来提取红曲的有效成分。
结果一:采用乙醇溶解、超声波振荡、在水浴氮气条件下使用旋转蒸发器的方法可以充分溶解红曲粉末,有效浓缩红曲醇提液。
方法二:采用去势骨质疏松的动物模型,以鲑鱼降钙素作为阳性对照,采用重复测量设计分析红曲对大鼠BMD、体重的影响。将6月龄雌性Wister大鼠32只随机分为四组,每组8只:假手术组(A组)、红曲组(B组)、降钙素组(C组)、模型组(D组);假手术组不摘除卵巢、切除卵巢周围少量脂肪组,余组切除双侧卵巢;术后1周开始药物干预,于1周末、6周末、12周末测量大鼠左侧股骨骨密度及体重;12周末处死动物,采用ELISA和紫外可见分光光度法分别观测大鼠OPG、ALP的表达,评价醇提红曲对去势大鼠的治疗效果。
结果二:1.骨密度:①不同干预因素各组间差异有统计学意义F=3.85 P=0.0199;测定时间之间的差异具有显著的统计学意义F=776.79 P＜0.0001;②多重比较:1周末、6周末四组总体均数无明显差异;12周末四组总体均数有明显差异:A组与B组、C组、D组的总体均数有差异,B组与A组、C组、D组的总体均数有差异,C组与A组、B组、D组的总体均数有差异,D组与A组、B组、C组的总体均数有差异。
2.体重:①不同干预因素各组间差异有统计学意义F=5.55 P=0.0041;测定时间之间的差异具有显著的统计学意义F=254.53 P＜0.0001;②多重比较:1周末、6周末四组总体均数无差异;12周末四组总体均数有差异,A组与B组、C组、D组的总体均数有差异,B组与A组的总体均数有差异,C组与A组的总体均数有差异,D组与A组的总体均数有差异,还不能认为B组、C组与D组的总体均数有差异。
3.OPG:各组间OPG总体均数有统计学差异F=5.29 P=0.0051;多重比较:说明A组与B组、C组、D组的OPG总体均数有差异,B组与A组、C组、D组的OPG总体均数有差异,C组与A组、B组、D组的OPG总体均数有差异,D组与A组、B组、C组的OPG总体均数有差异。
4.ALP:各组间ALP总体均数有统计学差异F=12.14 P＜0.0001;多重比较:说明A组与B组、D组的ALP总体均数有差异,B组与A组、C组、D组的ALP总体均数有差异,C组与B组、D组的ALP总体均数有差异,D组与A组、B组、C组的ALP总体均数有差异,还不能认为A组与C组的ALP总体均数有差异。
5.BMD值和OPG含量直线相关分析相关分析有统计学差异r=0.38167P=0.0311,BMD值和OPG含量之间存在正的直线相关关系。
6.OPG和ALP直线相关分析相关分析有统计学差异r=-0.10034 P=0.5848,OPG含量和ALP含量之间无直线相关关系。
7.BMD值和ALP含量直线相关分析相关分析有统计学差异r=-0.66048P＜0.0001,BMD值和ALP含量之间存在负的直线相关关系。
8.骨切片形态学观察:模型组股骨骨小梁大片消失,髓腔内残留纽扣样或棒状骨小梁结构,骨小梁连接断裂,排列疏松;假手术组股骨骨小梁结构呈网孔状,连接紧密,排列规则,骨小梁壁厚度一致。
结论:1.采用乙醇溶解、超声波振荡、在水浴氮气条件下使用旋转蒸发器的方法可以充分溶解红曲粉末,有效浓缩红曲醇提液。
2.模型组骨密度明显低于假手术组,股骨骨小梁大片消失,血清ALP含量明显高于假手术组,动物模型表现为骨量降低、骨微结构破坏、骨代谢高转换率,表明动物模型较为可靠。
3.实验结果证实红曲对去势大鼠骨密度值有一定的提高作用,可以有效降低去势大鼠的骨转换率、减缓由于雌激素分泌减少而造成的骨量减少,可用于绝经后骨质疏松的预防和治疗;BMD值与血清OPG含量存在正相关关系,说明大鼠骨密度下降与血清OPG含量降低有关;推测红曲其作用可能是通过改变血清OPG含量来实现的。
Objective:To explore the effects of Monascus on bone mineral density,weight,OPG and ALP in ovariectomized rats.To investigate the theraputic effects and mechanicms of Monascus in postmenop- ausal osteoporosis.
Methods1:According to modern pharmacological research findings,the use of ethanol solution, ultrasonic vibration,Bath nitrogen conditions to ethanol distilled to extract Monascus the active ingredients
Result1:Ethanol solution,ultrasonic vibration,Nitrogen in water bath for use rotary evaporator method can be fully dissolved Monascus powder,effective Concentration Monascus alcohol extract.
Methods2:Monascus was exaracted using dissolution of alcohol and vibration of ultrasound.Thirty- two female rats were rangomly divideded into four groups,8 in each:shame group-A group,Monascus group-B group,salmon calcitionin group-c group and ovariectomy group-d group.Bone mineral densities and weights of each group were measured at 1 week,6 week and 12 week after operation.The rats were killed at 12 week.OPG and ALP were measured by enzyme-linked immunosorbent assay and ulcraviolet-visible spectrophotometry.
Result2:1.BMD:①different factors of the intervention group are significantly different F=3.85 P=0.0199;Determination of the time difference was significant statistically significant F=776.79 P＜0.0001;②multiple comparisons:four groups in one weekend and six weekend overall mean no significant difference;In12 weekend there are significant differences:Group A is different from GroupB,GroupC and GroupD;Group B is different from Group A,Group C and GroupD;Group C is different from GroupA GroupB and GroupD;Group D is different from GroupA,GroupB and GroupC;
2.Weight:①different factors of the intervention group are significantly different F=5.55 P=0.0041;Determination of the time difference is significant statistically significant F=254.53 P＜0.0001;②multiple comparisons:Group A is different from GroupB GroupC GroupD;Group B is different from GroupA;Group C is different from GroupA;Group D is different from GroupA;there is no different among GroupB GroupC GroupD.
3.OPG:There is different between in four groups F=5.29 P=0.0051;multiple comparison:Group A is different from GroupB GroupC GroupD;Group B is different from GroupA GroupC GroupD;Group C is different from GroupA GroupB GroupD;Group D is different from GroupA GroupB GroupC;
4.ALP:There is different between in four groups F=12.14 P＜0.0001;multiple comp -arison:Group A is different from GroupB and GroupD;Group B is different from GroupA Group Cand GroupD;Group C is different from GroupB and GroupD;Group D is different from GroupA,GroupB and GroupC;
5.OPG and BMD of linear correlation analysis was statistically relevant difference r=0.38167 P=0.0311,there is a positive linear relationship between OPG and BMD.
6.OPG and ALPof linear correlation analysis was statistically different r=-0.10034 P=0.5848,there is no linear relationship between OPG and ALP.
7.BMD and ALP of linear correlation analysis was statistically relevant difference r=-0.66048 P＜0.0001,there is a negative linear relationship between BMD and ALP.
8.Bone biopsy morphology:the model group femurs large disappeared marrow remnant button or rod-like trabecular bone structure,trabecular bone connecting fracture,with osteoporosis;sham group femoral trabecular bone structure showed mesh-like connecting closely with the rules,trabecular thickness consistency.
Conclusion:1.Ethanol solution,ultrasonic vibration,Nitrogen in water bath for use rotary evaporator method can be fully dissolved Monascus powder,effective concentration Monascus alcohol extract.
2.BMD of model was lower than that of sham-operated group,femurs large disappear,serum ALP was significantly higher than that of the sham-operated group,animal model showed reduced bone mass and bone-destroying the structure,bone metabolism high conversion rate,animal models indicate more reliable.
3.The experimental results confirmed Monascus on BMD in ovariectomized rats with an increase,can effectively reduce the ovariectomized rat bone turnover rate,Slowed down due to reduced estrogen secretion caused by bone loss.Monascus can be used for postmenopausal osteoporosis prevention and treatment;s there is a positive correlation between the BMD and serum OPG level,There is a relationship between decreasement of rats bone mineral density and lowerment serum OPG levels.
引文
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[22]陈华,陈冠民.重复测量数据的方差分析与SAS程序实现.数理医药学杂志,2001,14(4):325-326
[23]赵晋芳,刘桂芬.重复测量资料分析常见统计错误与软件实现.现代预防医学,2002,29(3):314-316
[24]屠冠军,吕永利,范广宇,吕刚.切除卵巢大鼠胫、股骨不同部位的双能x线吸收法测量.中华骨科杂志,1998,18(9):559-560
[25]高飞,霍建忠.不同龄小鼠成骨细胞OPG和RANKL表达情况.中华风湿病学杂志,2005,9(4):219-221
[26]石少辉.去势大鼠胫骨形态计量学改变及骨髓基质细胞IL-1、IL-6、TNF-a、TGF-BmRNA 的表达:[硕士学位论文].天津:天津医科大学,2004
[27]杜建层,王健.他汀类药物抗骨质疏松作用机制的研究.《临床荟萃》,2005,20(4):237-238
[28]刘彦卿,宋永伟,张建福,冯坤,王健智,张灵菊,刘月桂,陈宝龙.中药骨必康防治去卵巢大鼠骨质疏松的实验研究.中医正骨,2001,13(7):6-8
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[30]谢新荣.OPG/RANK/RANKL系统与骨代谢的调节.医学文选,2004,23(6):800-802
[1]肖建德,等.实用骨质疏松学.科学出版社,2004.
[2]郝春华,商庆新.中医药防治原发性骨质疏松症研究现状.山东中医药大学学报,2004,28(2):153-156
[3]周玉芳,张茂良.特制医用调脂红曲的制备和药用价值.中国中医基础医学杂志,2000,6(3):37-38
[4]纪远中.红曲及红曲霉的研究现状及进展.天津药学,2004,17(2):65-67
[5]冯胜民,史美甫.他汀类药物非降脂作用临床研究进展.药学专论,2001,10(12):1-2
[6]杜建层,王健.他汀类药物抗骨质疏松作用机制的研究.《临床荟萃》,2005,20(4):237-238
[7]杜建层,周秀芹,庞义存,郭影.辛伐他汀对去卵巢大鼠血清IL-6、IGF-Ⅰ及成骨细胞BMP-2表达的影响.中国老年学杂志,2005,4(25):442-444
[8]卢建华,吴承亮,倪桂宝.红曲对去卵巢大鼠BMP-2表达及成骨细胞增殖影响的实验研究.中国骨伤,2005,18(1):25-27
[9]卢建华,吴承亮,王维佳.红曲对去势大鼠血清激素水平、骨密度和骨生物力学影响.中国中医骨伤科杂志,2004,12(4):20-23
[10]李永国,柳红,王峥涛.中药红曲化学稳定性多成分综合评价.高等学校化学学报,2006,27(1):35-38