Yi-Ling Chen1, Kuan-Hung Chen2, Tsung-Cheng Yin3, Tien-Hung Huang1, Chun-Man Yuen4, Sheng-Ying Chung1, Pei-Hsun Sung1, Meng-Shen Tong1, Chih-Hung Chen5, Hsueh-Wen Chang6, Kun-Chen Lin2, Sheung-Fat Ko7, Hon-Kan Yip8. 1. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan. 2. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan. 3. Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan. 4. Division of Neurosurgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan. 5. Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan. 6. Department of Biological Sciences, National Sun Yat-Sen University Kaohsiung, 80424, Taiwan. 7. Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan. 8. Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung, 83301, Taiwan; Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung, 83301, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiung, 83301, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical UniversityTaichung, 40402, Taiwan; Department of Nursing, Asia UniversityTaichung, 41354, Taiwan.
Abstract
BACKGROUND: We tested the hypothesis that extracorporeal shock wave (ECSW) therapy can effectively protect sciatic nerve (SN) from diabetes mellitus (DM)-induced neuropathy in leptin-deficient (ob/ob) mice. METHODS AND RESULTS: Eighteen-week C57BL/6 mice (n=8) served as age-matched controls (group 1) and ob/ob mice (n=16) were categorized into DM (group 2) and DM + ECSW (0.12 mJ/mm(2) for 4 times of 200 impulses at 3-week intervals) (group 3). The animals were sacrificed two weeks post-ECSW. In vitro results showed that the protein expressions of oxidative stress (NOX-1, NOX-2, oxidized protein), inflammation (MMP-9, TNF-α, iNOS), apoptosis (Bax, cleaved caspase-3, & PARP), and DNA-damage marker (γ-H2AX) were significantly higher in RT4-D6P2T (schwannoma cell line) treated by menadione (25 µM) compared with control group and were significantly reversed after ECSW (0.12 mJ/mm(2), 200 impulses) (all p<0.001). mRNA expressions of inflammation (MMP-9, TNF-α, iNOS), oxidative stress (NOX-1, NOX-2) and apoptosis (Bax, caspase-3) in SN were significantly higher in group 2 than in group 1 and were significantly reversed in group 3, whereas the mRNA expressions of anti-oxidants (HO-1, NQO1) progressively increased from group 1 to group 3 (all p<0.001). Cellular expressions of F4/80+, CD14+, γ-H2AX+ cells, and number of vacuolar formation in SN showed a pattern identical to that of inflammation markers among all groups (all p<0.001). Microscopic findings of Schwann cells and myelin-sheath scores, and number of eNOS+ cells in SN showed a reversed pattern compared to that of inflammation among all groups (all p<0.001). CONCLUSIONS: ECSW therapy protected SN against DM-induced neuropathy.
BACKGROUND: We tested the hypothesis that extracorporeal shock wave (ECSW) therapy can effectively protect sciatic nerve (SN) from diabetes mellitus (DM)-induced neuropathy in leptin-deficient (ob/ob) mice. METHODS AND RESULTS: Eighteen-week C57BL/6 mice (n=8) served as age-matched controls (group 1) and ob/ob mice (n=16) were categorized into DM (group 2) and DM + ECSW (0.12 mJ/mm(2) for 4 times of 200 impulses at 3-week intervals) (group 3). The animals were sacrificed two weeks post-ECSW. In vitro results showed that the protein expressions of oxidative stress (NOX-1, NOX-2, oxidized protein), inflammation (MMP-9, TNF-α, iNOS), apoptosis (Bax, cleaved caspase-3, & PARP), and DNA-damage marker (γ-H2AX) were significantly higher in RT4-D6P2T (schwannoma cell line) treated by menadione (25 µM) compared with control group and were significantly reversed after ECSW (0.12 mJ/mm(2), 200 impulses) (all p<0.001). mRNA expressions of inflammation (MMP-9, TNF-α, iNOS), oxidative stress (NOX-1, NOX-2) and apoptosis (Bax, caspase-3) in SN were significantly higher in group 2 than in group 1 and were significantly reversed in group 3, whereas the mRNA expressions of anti-oxidants (HO-1, NQO1) progressively increased from group 1 to group 3 (all p<0.001). Cellular expressions of F4/80+, CD14+, γ-H2AX+ cells, and number of vacuolar formation in SN showed a pattern identical to that of inflammation markers among all groups (all p<0.001). Microscopic findings of Schwann cells and myelin-sheath scores, and number of eNOS+ cells in SN showed a reversed pattern compared to that of inflammation among all groups (all p<0.001). CONCLUSIONS: ECSW therapy protected SN against DM-induced neuropathy.
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