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[丹参酮ⅡA通过调节TGF-β1/Smad2/MMPs信号通路改善去卵巢大鼠的软骨退变]

[Tanshinone ⅡA Ameliorates Cartilage Degeneration in Ovariectomized Rats by Regulating TGF-β1/Smad2/MMPs Signaling Pathway].

作者信息

Guo Qin, Guo Yuanli, Liao Feng'er, Tao Ying

机构信息

/ ( 510080) Department of Obstetrics and Gynecology, The First Affiliated Hospital/The First Clinical Medicine School of Guangdong Pharmaceutical University, Guangzhou 510080, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Jul 20;55(4):878-885. doi: 10.12182/20240760204.

DOI:10.12182/20240760204
PMID:39170014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11334281/
Abstract

OBJECTIVE

To investigate the ameliorative effect of tanshinone ⅡA (Tan) on osteoarticular degeneration in ovariectomized rats (a postmenopausal estrogen deficiency model) and the mechanisms involved.

METHODS

Eight-week-old female Sprague Dawley (SD) rats were randomly allocated to 5 groups (=10 each), including a Sham operation group (Sham), an ovariectomy group (OVX), and low, medium, and high-dose Tan groups. Eight weeks after bilateral ovariectomy, the rats in the low, medium, and high-dose Tan groups were treated with Tan at the doses of 5, 10, and 20 mg/kg for a duration of 28 days. Evaluation of the rat articular cartilage was performed using X-ray imaging, anatomical observation, hematoxylin and eosin (H&E) staining, and toluidine blue staining. Immunohistochemistry was performed to assess the expression levels of transforming growth factor β1 (TGF-β1), phosphorylated-smad2 (p-Smad2), type Ⅱ collagen (CⅡ), matrix metalloproteinase 9 (MMP-9), and MMP-13 in the cartilage tissue.

RESULTS

The knee joints of the OVX rats exhibited narrowed joint spaces, osteophyte formation, cartilage erosion or even localized cartilage cracks, faded methylene blue staining on the cartilage surface, disordered arrangement of chondrocytes, unclear or interrupted tidal line, and increased Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores compared to those of the Sham group (<0.01), as revealed by X-ray imaging, anatomical observation, and histological examination results. Tan ameliorated the degenerative changes in the knee joint caused by OVX in a dose-dependent manner while improving Kellgren-Lawrence grading, Pelletier grading, Mankin grading, and OARSI scores. Immunohistochemistry findings showed that TGF-β1, p-Smad2, and CⅡ expression levels were significantly increased (<0.01), while MMP-9 and MMP-13 expression levels were significantly decreased (<0.01) in the articular cartilage of the Tan group compared to those of the OVX group, with all these effects being dose-dependent.

CONCLUSION

Tan mitigates articular cartilage degeneration in ovariectomized rats, which may be related to the regulation of TGF-β1/Smad2/MMPs signaling pathway.

摘要

目的

探讨丹参酮ⅡA(Tan)对去卵巢大鼠(绝经后雌激素缺乏模型)骨关节退变的改善作用及其相关机制。

方法

将8周龄雌性Sprague Dawley(SD)大鼠随机分为5组(每组n = 10),包括假手术组(Sham)、去卵巢组(OVX)以及低、中、高剂量Tan组。双侧卵巢切除术后8周,低、中、高剂量Tan组大鼠分别给予5、10、20 mg/kg剂量的Tan治疗,持续28天。采用X线成像、解剖观察、苏木精-伊红(H&E)染色和甲苯胺蓝染色对大鼠关节软骨进行评估。通过免疫组织化学法检测软骨组织中转化生长因子β1(TGF-β1)、磷酸化Smad2(p-Smad2)、Ⅱ型胶原(CⅡ)、基质金属蛋白酶9(MMP-9)和MMP-13的表达水平。

结果

X线成像、解剖观察和组织学检查结果显示,与Sham组相比,OVX大鼠膝关节间隙变窄、有骨赘形成、软骨侵蚀甚至局部软骨裂纹,软骨表面亚甲蓝染色变淡,软骨细胞排列紊乱,潮线不清或中断,Kellgren-Lawrence分级、Pelletier分级、Mankin分级和OARSI评分增加(P < 0.01)。Tan能以剂量依赖性方式改善OVX所致的膝关节退变,同时改善Kellgren-Lawrence分级、Pelletier分级、Mankin分级和OARSI评分。免疫组织化学结果显示,与OVX组相比,Tan组关节软骨中TGF-β1、p-Smad2和CⅡ表达水平显著升高(P < 0.01),而MMP-9和MMP-13表达水平显著降低(P < 0.01),且所有这些作用均呈剂量依赖性。

结论

Tan可减轻去卵巢大鼠的关节软骨退变,这可能与调节TGF-β1/Smad2/MMPs信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/8550ce9916e2/scdxxbyxb-55-4-878-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/c2bdc78a58cd/scdxxbyxb-55-4-878-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/542c054e571a/scdxxbyxb-55-4-878-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/c6a4a8311129/scdxxbyxb-55-4-878-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/8550ce9916e2/scdxxbyxb-55-4-878-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/c2bdc78a58cd/scdxxbyxb-55-4-878-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/542c054e571a/scdxxbyxb-55-4-878-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/c6a4a8311129/scdxxbyxb-55-4-878-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3355/11334281/8550ce9916e2/scdxxbyxb-55-4-878-4.jpg

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