从“脾虚”方向探讨原发性骨质疏松症

　　骨质疏松症( osteoporosis,OP) 是一种以骨量低下,骨微结构损坏,导致骨脆性增加,易发生骨折为特征的全身性骨病.骨质疏松症可发生于不同性别和年龄,但多见于绝经后妇女和老年男性.骨质疏松症分为原发性、继发性和特发性 3 大类.原发性骨质疏松症又分为绝经后骨质疏松症( I 型) 和老年性骨质疏松症( II 型) 2 类.随着人类寿命延长和老龄化社会的到来,骨质疏松症已成为人类重要的健康问题[1].中医没有明确的"骨质疏松症"这一病名,但从本病的病因病机和临床症状上与中医古籍记载的"骨枯"、"骨痹"、"骨痿"、"骨极"等较为相似,它们与衰老和绝经均有密切关系.目前学界对骨质疏松症以肾虚为主要病机的观点达成普遍共识,形成以补肾滋肾为治疗总则的用药理论,并取得了一定的临床疗效.然而脾胃作为后天之本,气血生化之源,肾精亦须依赖脾精的滋养得以补充,故脾虚亦为本病的重要病机.本文从"脾虚"方向来探讨原发性骨质疏松症,为临床更好地诊治骨质疏松症拓宽思路,提高疗效.

　　1 传统医学对骨质疏松症的认识

　　《灵枢·经脉》云: "足少阴气绝则骨枯."《素问·长刺节论》云: "病在骨,骨重不举,骨髓酸痛,寒气至,名曰骨痹."《素问·痿论》云: "肾气热,则腰脊不举,骨枯而髓减,发为骨痿."《千金要方·骨极》云:"骨极者,主肾也,肾应骨,骨与肾合…若肾病则骨极,牙齿苦痛,手足疼,不能久立…故曰骨极."[2]《灵枢·决气》云: "谷入气满,淖泽注于骨."《素问·上古天真论》曰: "女子七岁骨气盛,齿更发长…四七筋骨坚,发长根,身体盛壮…七七…天癸竭,地道不通,故形坏而无子."《中藏经·五痹》云: "骨痹者,乃嗜欲不节,伤于肾也.肾气内消则不能关禁,……下流腰膝,则为不遂,旁攻四肢,则为不仁."这些从肾而论的观点为后世认识骨质疏松症奠定了理论基础.《灵枢·本神》云: "脾气虚则四肢不用."《素问·太阴阳明论》云: "今脾病不能为胃行其津液,四肢不得禀水谷气,气日以衰,脉道不利,筋骨肌肉,皆无气以生,故不用焉."《素问·五脏生成》所谓: "肾之合骨也,其荣在发,其主脾也."《素问·生气通天论》云: "是故谨和五味,骨正筋柔,气血以流,腠理以密,如是则骨气以精,谨道如法,长有天命."由此可见,脾虚在骨质疏松症的发病中起着重要的作用.

　　《诸病源候论·卷十五·五脏六腑病诸候》: "五谷五味之津液悉归于膀胱,气化分入血脉,以成骨髓也."宋代陈直《养老奉亲书·冬时摄养第十二》"高年阳气发泄,骨肉疏薄,易于伤动,多感外疾,惟早眠晚起,以避霜威","骨肉疏薄"的描述与现代对骨质疏松症的认识更为相似[3].张从正《儒门事亲》中描述: "皮痹不已,而成肉痹.肉痹不已,…而成骨痹",认为骨质疏松症的成因是渐进缓慢的发展过程.《医宗必读·痿》曰: "阳明虚则血气少,不能润养宗筋,故弛纵,宗筋纵则带脉不能收引,故足痿不用."李杲在《脾胃论·脾胃盛衰论》云: "脾病则下流乘肾,土克水,则骨乏无力,足为骨蚀,令人骨髓空虚."《医学发明·活法机要·虚损证》云: "虚损之疾,…自下而损者,一损损于肾,故骨痿不能起于床; 二损损于肝,故筋缓不能自收持; 三损损于脾,故饮食不能消克也.…脾胃损则谷不化也."这明确提出肾、肝和脾损也可致筋骨不利.王新祥等[4]认为李东垣《脾胃论》中有关"骨蚀"一病涵盖了骨质疏松症的范畴,"骨蚀"的病因病机是以脾虚为本,治则治法为益气升阳.朱小华等[5]从脾胃与肾、气血、肌肉骨骼、吸收消化等方面系统论述了脾胃与老年骨质疏松症的关系,提出健脾益胃是治疗老年骨质疏松症的一个重要方法.盛彤等[6]亦认为脾虚是原发性骨质疏松症的重要病因病机,在治则治法方面须重视补益脾胃.

　　2 原发性骨质疏松症的中医证型

　　辩证论治是中医的特色,中医药治疗骨质疏松症首先得辨析清楚它的中医证型,以便在诊治过程中做到有的放矢.原发性骨质疏松症中医辩证主要以脏腑辩证为主,大都责之于肾、肝、脾三脏.谢雁鸣等[7]根据临床流行病学调查和问卷调查的方法来探讨原发性骨质疏松症的证候因素和证候特征,结果显示原发性骨质疏松症的主要证候为肾阳虚证、肾精不足证、肾气虚证、肾阴阳两虚证、脾肾阳虚证、肾阴虚证和肝肾阴虚证,主要证候因素为阴虚、阳虚、气虚、气滞、湿浊和血瘀.原发性骨质疏松症是以肾、肝、脾三脏虚损为本,气滞、湿浊、血瘀为标的本虚标实之证.葛继荣等[8]认为肾虚是发生骨质疏松症的主要病因,肝、脾的亏虚多伴随肾虚,女性以肾阴虚多见,男性则多见肾阳虚.葛继荣等[9]的临床实验还证实维生素 D 受体基因 BsmⅠ多态性及中医证型分类与绝经后骨质疏松症骨密度存在相关性.杨洪彬等[10]对 91 例绝经后女性骨质疏松症进行中医证型辩证分析,发现其分布规律: 肝肾阴虚型 最 多 44 例 ( 48. 35%) ,肾 阴 虚 型 19 例( 20. 88%) ,肾阳虚型 12 例( 13. 19%) ,脾肾阳虚型10 例( 10. 99% ) ,脾胃虚弱型 6 例( 6. 59% ) .但通过单因素方差分析,各型骨量减少程度无显着性差异.方朝晖等[11]对 1000 例老年性骨质疏松症患者,根据中医理论分为 4 型进行分析归纳,共诊断出2857 个证次,平均每例患者存在 3. 86 个证候,4 个证候发生概率依次为瘀血阻络( 40. 8%) 、脾肾阳( 38. 5%) 、脾肾气虚( 35. 3%) 、肝肾阴虚( 23. 1%) .魏之玉等[12]认为骨的生长发育除了与肾有密切关系外,尚与肝、脾二脏关系密切,并根据临床表现将本病分为肾虚型、脾虚型、肝郁型和其它型共 4 型.

　　在收集的196 个病例中,肾虚型84 例,占42. 9%; 肝郁型 41 例,占 20. 9%; 脾虚型 50 例,占 25. 5%; 其他型 21 例,占 10. 7%.肾虚型所占比例最大,脾虚型其次,符合当前对原发性骨质疏松症的认识.以上结果表明,骨质疏松症的中医证型中脾虚是其中的一个重要证型,证候分型中脾肾两虚证占有较大比例.

　　3 健脾中药与骨质疏松症的关系

　　3. 1 单味健脾中药的研究

　　脾胃为后天之本,气血生化之源,后天元气的充养依赖于脾的健运,若脾胃虚弱,则肾失所养,因此健脾法是防治骨质疏松症的一种重要的治疗方法.

　　常用于治疗脾虚症状明显的骨质疏松症患者的药物包括人参、黄芪、升麻、白术、茯苓、大枣、甘草等健脾和胃,益气化湿[13].单味中药在防治骨质疏松症的实验研究中逐渐得到重视,黄芪是目前治疗骨质疏松症较多选用的一味中药.郭海玲等[14]实验表明不同浓度的黄芪可以明显促进成骨细胞的增殖,也可促进成骨细胞分泌I型胶原蛋白和上调COLLα1mRNA 的表达,以中高剂量黄芪促骨形成能力最佳,并指出治疗骨质疏松症时,选择中等剂量的黄芪有助于提高成骨细胞的增殖和骨形成能力.邹丽宜等[15]的实验指出黄芪对机体的性激素水平有提高作用,并且还能增强胃肠的吸收功能,提高骨密度.也有学者另辟蹊径,以药对方式研究,比如欧莉等[16]以熟地配伍黄芪为主药治疗绝经后骨质疏松症,结果表明能有效缓解其临床症状,提高骨密度,改善骨代谢,同时提高性激素水平.陈勇等[17]研究总黄酮 + 黄芪醇提物( 骨碎补 + 淫羊藿) 对实验性骨质疏松症小鼠骨代谢的影响,发现其对维甲酸所致小鼠骨质疏松症有一定的防治作用.曾高峰等[18]则是检索实验文献分析黄芪多糖对骨质疏松症模型大鼠的影响,得出黄芪多糖通过调节骨钙素和抗酒石酸酸性磷酸酶的表达活性发挥治疗骨质疏松症的作用.另外还有一些其他的健脾药物如山药、泽泻、茯苓,山药能增加小肠吸收功能,保证促进骨形成的营养物质充足,并对血糖升高有一定的预防作用,防止老年人因血糖升高导致的骨质疏松症.

　　泽泻水提醇沉物( RAE) 具有降血糖作用,并保护胰岛组织免受损伤,从而预防骨质疏松症的发生.茯苓能增强脾肾功能,加强对钙质等的吸收,且健脾药本身即含多种氨基酸及锌,因而有利于骨形成[19].

　　3. 2 健脾复方的实验研究

　　有作者动物实验证明了健脾方药( 党参、白术、黄芪、当归、熟地黄、炮附子等) 对骨质疏松症大鼠骨代谢指标中的血清碱性磷酸酶( ALP) 、尿钙与尿肌酐比值( Ca/Cr) 、尿磷与尿肌酐比值( P/Cr) 、尿羟脯氨酸 P 与尿肌酐比值( HOP/Cr) ,以及维生素 D代谢起着重要作用,可有效防治骨质疏松[20-21].邹本贵[22]对骨质疏松症大鼠骨组织形态研究结果显示参归促钙灵( 人参、当归、山药、白术、薏苡仁、砂仁、陈皮等) 联合葡萄糖酸钙、雌激素联合葡萄糖酸钙均能显着增加骨小梁体积密度及表面积密度,升高成骨细胞指数,降低破骨细胞指数,两组比较差异无统计学意义.参归促钙灵联合葡萄糖酸钙、雌激素联合葡萄糖酸钙既能抑制骨吸收,又能刺激成骨细胞产生更多的骨基质,使骨代谢转为正平衡,使丢失的骨量得到一定程度的恢复,从而有效地阻止骨质疏松症的发展.现代临床研究也证明应用健脾益气养胃方药可以促进 1,25( OH)2D3的生成,促进肠道对钙、磷等微量元素、氨基酸及蛋白质等营养物质的吸收[23-24].因此,脾脏的功能发挥与骨质疏松症的发生有着重要的关联.

　　4 补肾健脾法与骨质疏松症的关系

　　4. 1 补肾健脾法的实验研究

　　脾与肾是后天与先天的关系,二者相互资助、相互促进,在病理上又能相互影响、互为因果.肾虚被看作是骨质疏松症发生的根本原因,是其基本病机;脾虚是骨质疏松症发生的重要因素,是其重要病机.

　　过去中医药治疗骨质疏松症常注重补肾而忽略健脾,影响了中医药对骨质疏松症治疗的进一步提高.

　　有不少学者对补肾健脾与骨质疏松症的相关性做了大量的实验研究.早前李涯松等[25]做的动物实验用到补中益气汤合右归饮,结果表明以健脾加补肾方来防治老龄大鼠骨质疏松症较单用补中益气汤或右归饮效果更佳.倘艳锋等[26]的研究结果同样表明补肾健脾法能够有效地防治骨质疏松症.鞠大宏等[27]对大鼠脾肾两虚型骨质疏松症的研究说明健脾法、补肾法和补肾健脾法对脾肾两虚型大鼠骨质疏松症均具有治疗作用,其中补肾健脾法的效果最佳.刘文轩等[28]将去卵巢大鼠骨质疏松模型随机分组,测量各组的子宫内膜厚度,测定血清钙、磷、碱性磷酸酶、性激素、骨钙素水平等代谢指标,发现运脾滋肾汤可防治卵巢切除所致骨量丢失.孙鑫等[29]对去卵巢大鼠骨质疏松症模型分别给予补肾和健脾的中药灌胃 3 个月,Western blotting 法检测指标,结果发现补肾、健脾中药均可下调模型大鼠下丘脑中 PKCα 与 PKCβ2蛋白表达( P < 0. 01) ,补肾中药防治骨质疏松症的作用优于健脾中药.

　　4. 2 补肾健脾法的临床研究

　　补肾健脾与骨质疏松症的临床观察和临床研究亦不少,周立飞等[30]将绝经后骨质疏松症( POP) 患者 80 例分两组,40 例给予降钙素和钙天力治疗,40例在此基础上加用补肾健脾汤,治疗前后进行骨密度测定,并进行组血清 E2及细胞因子 TNF-a、IL-4、IL-6、IGF-1 的测定,最后得出补肾健脾汤对 POP 有肯定疗效.一些作者[31-34]在他们的临床实验疗效观察中,运用补肾健脾方药作为治疗组治疗骨质疏松症患者均明显优于对照组,存在显着性差异,治疗组均取得满意效果,患者临床症状明显得到改善,提示补肾健脾的疗效优于单纯的补肾或健脾或西药的疗效.也有从基因表达水平上研究肾虚型骨质疏松症[35-37],探寻骨质疏松症患者相关基因的易感性,从微观角度为骨质疏松症的治疗提供依据.由此,今后运用中医中药治疗骨质疏松症患者时,在用补肾方法治疗的同时,辅以健脾的方法,实现健脾实肌肉、补肾壮骨骼的脾、肾同治的治疗目的,以期更加有效地防治骨质疏松症.

　　5 小结

　　根据中医学对骨质疏松症病因病机特点的认识,结合现代医学对中医药治疗骨质疏松症的研究,对骨质疏松症的防治要按照中医的理法方药进行辩证论治,因证施治,不能简单地治疗某一脏一腑,要看到骨质疏松症的复杂性和难治性.从传统医学中脾对骨质疏松症的认识到脾脏与骨质疏松症关系的实验研究再到健脾补肾的临床观察,无不表明脾虚在原发性骨质疏松症的重要地位.肾虚为骨质疏松症的主要病机,补肾滋肾的治疗总则固然重要,与此同时必须要重视补益脾胃.在治疗中要以肾为根本,以脾胃为基础.以发挥中医药治疗的优势,更好的防治骨质疏松症.随着生命科学技术的发展和研究水平的提高,现代医学关于骨质疏松症的研究已经深入到基因蛋白水平,从基因层次进行中医药治疗骨质疏松症作用机制的研究,探寻骨质疏松症患者易感基因,从人体的基因蛋白上破解骨质疏松症这一难题,将成为一种趋势.

　　【 参 考 文 献 】

　　[1] The Chinese medical association of osteoporosis and bone mineralsalt disease branch. Guide for diagnosis and treatment of primaryosteoporosis( 2011 ) . Chinese Journal of osteoporosis and bonemineral diseases,2011,4( 1) : 2-17.

　　[2] ZHANG Ying,ZHANG Bo,ZHANG Zhiguo,et al. From the liverand spleen kidney three zang to explore the pathogenesis ofpostmenopausal osteoporosis. Chinese Journal of Basic Medicinein Traditional Chinese Medicine,2012,18( 1) : 36-42.

　　[3] XU Quiqi. The ancient literature to the understanding of theetiology and pathogenesis of osteoporosis. Journal of traditionalChinese medicine,2008,49( 6) : 268-269.

　　[4] WANG Xinxiang,ZHANG Yunling,WANG Shaojie. Osteoporosisand recognition of bone erosion by LI Dong-yuan. Journal ofBeijing University of Traditional Chinese Medicine,2009,32( 7) :446-449.

　　[5] ZHU Xiaohua,ZHAO Canghuan. From the spleen and stomachtreatment of osteoporosis. Journal of New Chinese Medicine,2004,36( 12) : 3-4.

　　[6] SHENG Tong,XIE Peifeng,WANG Xinxiang. TCM treatment ofosteoporosis by nourishing spleen essence and discussions ofmechanism. Journal of Chinese medicine,2012,27 ( 7 ) : 1922-1926.

　　[7] XIE Yanming,ZHU Yunyin,GE Jirong,et al. Based on clinicalepidemiological investigation of primary osteoporosis basicsyndromes of TCM research. The world science and technology /Modernization of Traditional Chinese Medicine and MateriaMedica,2007,9( 2) : 38-44.

　　[8] GE Jirong,CHEN Ke,WANG Heming. Primary osteoporosis ofsyndrome differentiation of TCM research. Journal of fujiancollege of traditional Chinese medicine,2005,15( 1) : 9-11.

　　[9] GE Jirong,LI Shengqiang,ZHU Xiaoxiang,et al. Bsm Ipolymorphism of vitamin D receptor gene and traditional Chinesemedicine differentiation type in relation to bone mineral density infemale patient with postmenopausal osteoporosis. Chinese Journalof Clinical Rehabilitation,2006,10( 15) : 42-44.

　　[10] YANG Hongbin,XU Zujian,WANG Xinxiang,et al. Study onTCM Syndrome Patterns and Distribution of PostmenopausalOsteoporosis in South Sichuan. Journal of Sichuan of TraditionalChinese,2009,27( 4) : 23-25.

　　[11] FANG Zhaohui,GENG Jiajin,ZHANG Youzhi,et al. Study ondistribution and grouping regularity of TCM syndrome in 1000cases of senile osteoporosis. Chinese Journal of information onTCM,2007,14( 5) : 15-17.

　　[12] WEI Zhiyu,ZHANG Hong,ZHU Zhenduo. 196 cases of primaryosteoporosis dialectical analysis. Journal of shandong college ofTCM,1996,20( 1) : 30-31.

　　[13] ZHAO Dong,ZHANG Boxin,DAI Qi. Advances of internalChinese medical therapy in senile osteoporosis. China practicalmedicine,2010,5( 27) : 244-246.

　　[14] GUO Hailing,WANG Xiang,XU Yu,et al. Astragalus rootinjection regulates typeI collagen expression of rat osteoblasts invitro. Journal of Clinical Rehabilitative Tissue EngineeringResearch,2010,14( 7) : 1257-1261.

　　[15] ZOU Liyi,WU tie,CUI liao,et al. Astragalus root polysaccharideon liver fibrosis prevention and treatment of bone loss in mice.Chinese Journal of Integrated Traditonal and Western Medicine onLiver Diseases,2002,12( 2) : 95-98.

　　[16] OU Li,ZENG Xiaohong,ZHAO Peng. Mainly prepared rhizomeof rehmannia,astragalus medicine clinical observation for thetreatment of postmenopausal osteoporosis. Beijing Journal ofTCM,2011,30( 8) : 605-606.

　　[17] CHEN Yong,XIAO Ruanmei,DU Peng. Effects of the mixture ofEpimediem sagittatum flavone,Rhizoma Drynariae flavone and theenthanol extract of Astragalus variabills Bunge on osteoporosismice induced by retinoic acid. Journal of hubei university:natural science,2007,29( 2) : 189-191,195.

　　[18] ZENG Gaofeng,ZHANG Zhiyong,LU Li,et al. Effect andmechanism of polysaccharide intervention in a rat model ofosteoporosis. Chinese Journal of Tissue Engineering Research,2012,16( 50) : 9471-9478.

　　[19] LIU Haiye,YE Ze,DENG Weimin. Traditional Chinese medicinetreatment of senile osteoporosis. Chinese Journal of Gerontology,2009,29( 4) : 500-502.

　　[20] ZHANG Yuhui,LV Yinjuan,CHEN Jiuyi. Tonifying Spleen foursupplementation on bone metabolism in aged male rats withosteoporosis impact. Hubei journal of traditional Chinesemedicine,2006,28( 6) : 7-8.

　　[21] WANG Xiang,ZHAO Yongfang,SHI Yingyu,et al. The Effects ofJianPi prescription on vitamin D3metabolism in ovariectomizedrats. Chinese Journal of Osteoporosis,2007,13 ( 6 ) : 429-432,413.

　　[22] ZOU Bengui,LIU Hongqi. Effect of Spleen-nourishing Herbs onMorphous of Bone Tissue of Rats with Osteoporosis. Journal ofshanxi college of traditional Chinese medicine,2009,10( 1) : 11-12,22.

　　[23] YANG Zhao,YANG Hua,YAO Zhenqiang,et al. The stimulativeeffect of Kidneys-tonifying Chinese meterdia medica on ER andOPG expressions in lumbar vertebrae of ovariectomized rat. TheJournal of Traditional Chinese Orthopedics and Traumatology,2004,16( 3) : 131-133.

　　[24] LI Ang,XIAO Jinfu,XUE Ting,et al. Osteoporosis and nitricoxide. Chinese Journal of Pathophysiology,2001,17 ( 2 ) : 174-179.

　　[25] LI Yasong,TONG Peijian,MA Hongzhen,et al. Effects of spleen-strengthening and kidney-tonifying traditiona Chinese herbalmedicine on osteoporosis in aged rats. Chinese journal ofosteoporosis,2003,9( 2) : 167-170.

　　[26] TANG Yanfeng,CHEN Jiuyi,LI Yuxiong,et al. Effect of theMethod of Bu Shen Jian Pi on Bone Histoncorphometry inOsteoporosis Rats. Lishizhen Med Mat Med Res,2009,20 ( 2 ) :287-288.

　　[27] JU Dahong,LI Honghong,LIU Hong,et al. Therapeutic effect ofrecuperating kidney and invigorating spleen prescription on ratswith osteoporosis of spleen and kidney deficiency syndrome. ChinaJournal of Traditional Chinese Medicine and Pharmacy,2012,27( 12) : 3207-3210.

　　[28] LIU Wenxuan,WANG Xuchu,ZHAO Xiaohui,et al. Effect ofYunpi Zishen Decoction on Osteoporosis in Ovariectomized Rats.Chinese Archives of Traditional Chinese Medicine,2011,29( 11) : 2561-2563.

　　[29] SUN Xin,ZHENG Hongxin,YAN Yan,et al. Effects of BushenJianpi Recipe on Expression of PKC Protein in Hypothalamus inrats with Osteoporosis. Chinese Journal of Basic Medicine inTraditional Chinese Medicine,2010( 5) : 387-389.

　　[30] ZHOU Lifei,GAO Xiaobo,LIU Zhendong. Effects of tonifyingkidney and spleep decoction on cellular factors,bone mineraldensity and E2level in post menopausal osteoporosis patients.Chinese Journal of Traditional Medical Science and Technology,2008,15( 3) : 170-171,159.

　　[31] LAO Ruiping,SUN Guihe,SUN Yanhong. Tonifying kidney,strengthening spleen and activating blood circulation in patientswith postmenopausal osteoporosis effect of bone alkalinephosphatase. Guangming Journal of Chinese Mddicine,2012,27( 10) : 1983-1984.

　　[32] HU Jie,LI Ceng. Clinical Observation of Bu Shen Jian PiTreatment of Primary Osteoporosis. Hubei journal of traditionalChinese medicine,2012,34( 4) : 11-12.

　　[33] LUO Yannan,XUE Chuanjiang. clinical observation onStrengthening the spleen and tonifying the kidney in treatingpostmenopausal osteoporosis. Chinese journal of Chinesemedicine information,2012,19( 6) : 78-79.

　　[34] HUANG Zhisheng,BAI Yanfu. Support kidney fortify qistrengthen bone plaster on bone mineral density in patients withpostmenopausal osteoporosis and the effects of cytokines. GuidingJournal of Traditional Chinese Medicine and Pharmacology,2012,18( 3) : 25-26.

　　[35] GE Jirong,XIE Lihua,CHEN Ke,et al. Analysis of differentialexpression genes in Postmenopausal osteoporosis patients withkidney-Yang deficiency. Chinese Journal of Osteoporosis,2012,18( 2) : 134-138.

　　[36] XIE Lihua,ZHAO Yipeng,GE Jirong,et al. Bioinformaticsanalysis of genes expression profiles of postmenopausalosteoporosis with Kidney yin deficiency. Journal of ClinicalRehabilitative Tissue Engineering Research,2011,15( 15) : 2833-2837.

　　[37] GE Jirong,CHEN Ke,XIE Lihua,et al. The relationship betweenApaI polymorphism of VDR gene and bone mineral density inpostmenopausal women. Chinese Journal of Osteoporosis,2010,16( 10) : 719-722.