Effects of simvastatin‑loaded PLGA microspheres on treatment of rats with intervertebral disk degeneration and on 6‑K‑PGF1α and HIF‑1α

Zhu,Kai; Zhao,Futing; Yang,Yanhua; Mu,Weidong

doi:10.3892/etm.2019.8267

Effects of simvastatin‑loaded PLGA microspheres on treatment of rats with intervertebral disk degeneration and on 6‑K‑PGF1α and HIF‑1α

Authors:
- Kai Zhu
- Futing Zhao
- Yanhua Yang
- Weidong Mu
View Affiliations

Affiliations: Department of Traumatic Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Orthopedics, Qingyun County People's Hospital, Dezhou, Shandong 253700, P.R. China, Department of Pathology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
Published online on: December 2, 2019 https://doi.org/10.3892/etm.2019.8267
Pages: 579-584
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Effects of simvastatin‑loaded PLGA sustained release microspheres on the treatment of rats with intervertebral disk degeneration (IVDD) and on 6‑keto‑prostaglandin F1α (6‑K‑PGF1α) and hypoxia inducible factor‑1α (HIF‑1α) were investigated. Eighty female rats were selected and randomized into a model group (modeled for IVDD), a treatment group (modeled and treated with simvastatin‑loaded PLGA sustained release microspheres), a sham operation group (only operated without excision), and a control group (not treated) (n=20 each). After modeling, 6‑K‑PGF1α and HIF‑1α in the peripheral blood of the rats were, respectively, detected before simvastatin injection (T0), at 2 weeks (T1) and 4 weeks (T2) after simvastatin injection. The bone mineral density (BMD) of L5 and L6 was detected by X‑ray. The trabecular thickness, number, and separation of the vertebral body were detected. Changes in the sagittal T2‑weighted signal of intervertebral disc nucleus pulposus were detected by MRI. There were no differences between the control and sham operation groups in the indices (P>0.050). Compared with those in the model group during the treatment, BMD, 6‑K‑PGF1α, HIF‑1α, and trabecular number in the treatment group significantly increased (P<0.050), while the trabecular separation significantly decreased (P<0.050). The sagittal T2‑weighted MRI signal in the model group was the lowest between the four groups (P<0.050). Simvastatin‑loaded PLGA sustained release microspheres can improve the BMD of the vertebral body and increase the contents of 6‑K‑PGF1α and HIF‑1α in the treatment of rats with IVDD, so they are important for the clinical treatment of the disease.

View Figures

View References

1	Feng C, Liu H, Yang M, Zhang Y, Huang B and Zhou Y: Disc cell senescence in intervertebral disc degeneration: Causes and molecular pathways. Cell Cycle. 15:1674–1684. 2016. View Article : Google Scholar : PubMed/NCBI
2	Feng Y, Egan B and Wang J: Genetic factors in intervertebral disc degeneration. Genes Dis. 3:178–185. 2016. View Article : Google Scholar : PubMed/NCBI
3	Wang F, Cai F, Shi R, Wang XH and Wu XT: Aging and age related stresses: A senescence mechanism of intervertebral disc degeneration. Osteoarthritis Cartilage. 24:398–408. 2016. View Article : Google Scholar : PubMed/NCBI
4	Zhang F, Zhao X, Shen H and Zhang C: Molecular mechanisms of cell death in intervertebral disc degeneration (Review). Int J Mol Med. 37:1439–1448. 2016. View Article : Google Scholar : PubMed/NCBI
5	Sun D, Liu P, Cheng J, Ma Z, Liu J and Qin T: Correlation between intervertebral disc degeneration, paraspinal muscle atrophy, and lumbar facet joints degeneration in patients with lumbar disc herniation. BMC Musculoskelet Disord. 18:1672017. View Article : Google Scholar : PubMed/NCBI
6	Corniola MV, Stienen MN, Joswig H, Smoll NR, Schaller K, Hildebrandt G and Gautschi OP: Correlation of pain, functional impairment, and health-related quality of life with radiological grading scales of lumbar degenerative disc disease. Acta Neurochir (Wien). 158:499–505. 2016. View Article : Google Scholar : PubMed/NCBI
7	Zeckser J, Wolff M, Tucker J and Goodwin J: Multipotent mesenchymal stem cell treatment for discogenic low back pain and disc degeneration. Stem Cells Int. 2016:39083892016. View Article : Google Scholar : PubMed/NCBI
8	Sakai D and Schol J: Cell therapy for intervertebral disc repair: Clinical perspective. J Orthop Translat. 9:8–18. 2017. View Article : Google Scholar : PubMed/NCBI
9	Chen K, Lv X, Li W, Yu F, Lin J, Ma J and Xiao D: Autophagy is a protective response to the oxidative damage to endplate chondrocytes in intervertebral disc: implications for the treatment of degenerative lumbar disc. Oxid Med Cell Longev. 2017:40417682017. View Article : Google Scholar : PubMed/NCBI
10	Ye S, Ju B, Wang H and Lee KB: Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration. Bone Joint Res. 5:412–418. 2016. View Article : Google Scholar : PubMed/NCBI
11	Dai L, Xu M, Wu H, Xue L, Yuan D, Wang Y, Shen Z, Zhao H and Hu M: The functional mechanism of simvastatin in experimental osteoporosis. J Bone Miner Metab. 34:23–32. 2016. View Article : Google Scholar : PubMed/NCBI
12	Elkadi S, Elsamaligy S, Al-Suwayeh S and Mahmoud H: The development of self-nanoemulsifying liquisolid tablets to improve the dissolution of simvastatin. AAPS PharmSciTech. 18:2586–2597. 2017. View Article : Google Scholar : PubMed/NCBI
13	Steinbach JM, Seo YE and Saltzman WM: Cell penetrating peptide-modified poly(lactic-co-glycolic acid) nanoparticles with enhanced cell internalization. Acta Biomater. 30:49–61. 2016. View Article : Google Scholar : PubMed/NCBI
14	Zhang C, An T, Wang D, Wan G, Zhang M, Wang H, Zhang S, Li R, Yang X and Wang Y: Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma. J Control Release. 226:193–204. 2016. View Article : Google Scholar : PubMed/NCBI
15	Chen J, Xuan J, Gu YT, Shi KS, Xie JJ, Chen JX, Zheng ZM, Chen Y, Chen XB, Wu YS, et al: Celastrol reduces IL-1β induced matrix catabolism, oxidative stress and inflammation in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration in vivo. Biomed Pharmacother. 91:208–219. 2017. View Article : Google Scholar : PubMed/NCBI
16	Liu J, Tao H, Wang H, Dong F, Zhang R, Li J, Ge P, Song P, Zhang H, Xu P, et al: Biological behavior of human nucleus pulposus mesenchymal stem cells in response to changes in the acidic environment during intervertebral disc degeneration. Stem Cells Dev. 26:901–911. 2017. View Article : Google Scholar : PubMed/NCBI
17	Gentile P, Nandagiri VK, Daly J, Chiono V, Mattu C, Tonda-Turo C, Ciardelli G and Ramtoola Z: Localised controlled release of simvastatin from porous chitosan-gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application. Mater Sci Eng C. 59:249–257. 2016. View Article : Google Scholar
18	Ramazani F, Chen W, van Nostrum CF, Storm G, Kiessling F, Lammers T, Hennink WE and Kok RJ: Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: State-of-the-art and challenges. Int J Pharm. 499:358–367. 2016. View Article : Google Scholar : PubMed/NCBI
19	Terauchi M, Inada T, Tonegawa A, Tamura A, Yamaguchi S, Harada K and Yui N: Supramolecular inclusion complexation of simvastatin with methylated β-cyclodextrins for promoting osteogenic differentiation. Int J Biol Macromol. 93:1492–1498. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zhang P, Han F, Li Y, Chen J, Chen T, Zhi Y, Jiang J, Lin C, Chen S and Zhao P: Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament. Int J Nanomedicine. 11:465–478. 2016. View Article : Google Scholar : PubMed/NCBI
21	Russell-Puleri S, Dela Paz NG, Adams D, Chattopadhyay M, Cancel L, Ebong E, Orr AW, Frangos JA and Tarbell JM: Fluid shear stress induces upregulation of COX-2 and PGI₂ release in endothelial cells via a pathway involving PECAM-1, PI3K, FAK, and p38. Am J Physiol Heart Circ Physiol. 312:H485–H500. 2017. View Article : Google Scholar : PubMed/NCBI
22	Mayoral-Andrade G, Pérez-Campos-Mayoral L, Majluf-Cruz A, Perez-Campos Mayoral E, Perez Campos Mayoral C, Rocha-Núñez A, Martinez M, Zenteno E, Hernandez-Gonzalez L, López Juan MG, et al: Reduced platelet aggregation in women after intercourse: A possible role for the cyclooxygenase pathway. Clin Exp Pharmacol Physiol. 44:847–853. 2017. View Article : Google Scholar : PubMed/NCBI
23	Fan H, Li M, Yu L, Jin W, Yang J, Zhang Y and Wan H: Effects of Danhong injection on platelet aggregation in hyperlipidemia rats. J Ethnopharmacol. 212:67–73. 2018. View Article : Google Scholar : PubMed/NCBI
24	Mok FPS, Samartzis D, Karppinen J, Fong DY, Luk KD and Cheung KM: Modic changes of the lumbar spine: Prevalence, risk factors, and association with disc degeneration and low back pain in a large-scale population-based cohort. Spine J. 16:32–41. 2016. View Article : Google Scholar : PubMed/NCBI
25	Chiang CH, Chu PY, Hou MF and Hung WC: MiR-182 promotes proliferation and invasion and elevates the HIF-1α-VEGF-A axis in breast cancer cells by targeting FBXW7. Am J Cancer Res. 6:1785–1798. 2016.PubMed/NCBI
26	Balamurugan K: HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer. 138:1058–1066. 2016. View Article : Google Scholar : PubMed/NCBI
27	Huang TH, Chung SY, Chua S, Chai HT, Sheu JJ, Chen YL, Chen CH, Chang HW, Tong MS, Sung PH, et al: Effect of early administration of lower dose versus high dose of fresh mitochondria on reducing monocrotaline-induced pulmonary artery hypertension in rat. Am J Transl Res. 8:5151–5168. 2016.PubMed/NCBI
28	Hong F, Wang X and Tu G: Underlying mechanism of effect of Shenfu injection on Buerger's disease model rats. 2011 International Conference on Human Health and Biomedical Engineering IEEE. 1041–1044. 2011. View Article : Google Scholar