中国骨质疏松杂志

小鼠非酒精性脂肪肝纤维化对骨微结构的影响及姜黄素治疗作用

Effects of nonalcoholic fatty liver fibrosis on bone microstructure in mice and the therapeutic effect of curcumin

DOI：10.3969/j.issn.1006-7108.2021.04.003

英文关键词:NAFLD liver fibrosis curcumin bone microstructure BMD

基金项目:

作者	单位
王铜浩1* 唐飞2 田永刚1 陈志清1 郑金鑫1	1.天津市人工细胞工程技术研究中心；天津市重症疾病体外生命支持重点实验室；天津市肝胆疾病研究所；天津市第三中心医院骨科，天津 300170 2.天津市第三中心医院消化科/肝内科，天津 300170

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中文摘要:

目的探讨非酒精性脂肪肝（NAFLD）小鼠模型肝纤维化对骨微结构影响及姜黄素的治疗作用。方法 6周龄雌性野生型C57BL/6小鼠30只，随机分为野生小鼠对照组(WT组，n=10)，高脂饮食组(HFD组，n=10)和姜黄素治疗组(HFD+Cur组n=10)。对照组给予普通饲料饲养，高脂饮食组给予高脂饮食饲养，姜黄素治疗组除了给予高脂饮食外，在24周时给予姜黄素治疗。各组小鼠于32周末处死，检测小鼠血清生化指标，以及小鼠血清中TNF-α，IL-6，IGF-1和IGFBP-1的水平，肝组织HE染色后进行光镜病理学检测，micro-CT分析骨微结构及骨密度。结果与WT组相比，HFD组血清中AST、IL-6、TNF-α明显升高(P＜0.05)，而体重、TC、ALT、IGF-1、IGFBP-1变化更加明显（P＜0.01）；小鼠肝组织纤维化增生明显，同时胫骨近端参数BV/TV、Tb.Th、Tb.N、Tb.Sp、Conn.D/mm3、C.Th、vBMD、tBMD及骨干形态与WT组相比差异具有统计学意义（P＜0.05、P＜0.01）；通过姜黄素治疗后除IGF-1水平明显升高(P＜0.05)，小鼠体重以及血清中其余各指标水平明显下降(P＜0.05)，更接近于WT组（P>0.05）；肝脏病理学未见明显坏死灶及纤维化，小鼠骨微结构参数及骨干形态较HFD组明显好转（P＜0.05、P＜0.01），部分参数接近WT组（P>0.05）。结论小鼠非酒精性脂肪肝纤维化期可出现明显骨量丢失，血清中TNF-α、IL-6、IGF-1和IGFBP-1变化在其发病机制中起到重要的作用，其中IGF-1和IGFBP-1作用尤为重要，而姜黄素通过调节这些细胞因子可减轻脂质聚集，增加骨小梁、骨皮质及骨密度。

英文摘要:

Objective The present study aims to investigate the potential effects of liver fibrosis on bone microstructure in mice with nonalcoholic fatty liver (NAFLD) disease and the therapeutic effect of curcumin. Methods Six-week-old wild-type C57BL/6 female mice were randomly assigned to three groups: wild-type C57BL/6 mice control group (WT group, n=10), wild-type C57BL/6 mice with a HFD (HFD group, n=10) and HFD with curcumin (HFD+Cur group, n=10). The control group was fed with normal diet, the high-fat diet group was fed with high-fat diet, and the curcumin treatment group was treated with curcumin at 24 weeks. Mice in each group were sacrifced at 32 weeks and serum biomarkers and the cytokines TNF-α, IL-6, IGF-1, and IGFBP-1 were determined, hematoxylin and eosin staining of liver sections revealed hepatic steatosis, and micro-CT scans were made of the proximal tibia. Results Compared with the WT group, the AST, IL-6 and TNF-α levels were significantly higher in the HDF group (P<0.05), while the differences of weight, TC, ALT, IGF-1, IGFBP-1 were even greater (P<0.01). Meanwhile, the mouse in the HFD group liver tissue showed obvious fibrosis and the bone microstructure parameters of BV/TV, Tb.Th, Tb.N, Tb.Sp, Conn.D.mm-3, C.Th, vBMD, tBMD displayed a significantly differences compared with WT group (P<0.05 or P<0.01). After treatment with curcumin, except the IGF-1 level was significantly increased (P<0.05), the body weight of the mice and the serum levels of other indicators were significantly decreased (P<0.05), which was more similar to that of the WT group (P>0.05). Meanwhile, no obvious liver fibrosis were observed in liver pathology, and there were significantly increases in trabecular bone mass of the metaphysis as well as clearly improved BMD (P<0.05 or P<0.01). Conclusion Significant bone loss can be observed in mice with nonalcoholic fatty liver fibrosis, and the changes of the TNF-α, IL-6, IGF-1, and IGFBP-1 levels may play critical roles in pathogenesis, among which IGF-1 and IGFBP-1 play a particularly important role. Curcumin, by regulating these cytokines, can reduce lipid accumulation and increase bone trabeculae, bone cortex and bone mineral density.

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