| Background and significanceChina has already entered into the aging society in the turn of the century. Nowadays, there have been nearly 160 million of the aged over 60 years old. Our country has the most of the aging population in the world. Knee Osteoarthritis (KOA) is the commonest chronic osteoarticular disease of the ages and it is common in clinic. The concept of KOA was firstly proposed by Garrod in 1890. In 1909, Nichols and RichMdDn found that main pathological features of KOA included retrogressive changes of joints. From the perspective of modern medicine, it shows that KOA is a all-dimensional and multi-level chronic inflammation with varying degree and it has the core of retrogressive cartilage articularis and involves in the entire joints, including subchondral bone, ligament, joint capsule, synovial and muscles around joints. The leading clinical symptoms reflect in knee pain and unstable joints.Lots of studies on pathogenesis of osteoarthritis show that the occurrence of KOA is mainly caused by the degradation of cartilage matrix and obvious synthetic unbalance. The main pathologic changes mean to destroy collagen in cartilage articularis matrix and progressive apoptosis of cartilage cells. Matrix metalloproteinases (MMPs) generated by human cartilage cells is the most important protein hydrolysis system of extracellular matrix (ECM) degradation. MMP-13 is the most effective type II collagen degradation enzyme in family members of MMPs, especially for the pathological state. Cartilage cells generate lots of MMPs, degrade type II collagen, result in running off protein polysaccharide and cause cartilage destroy and defects, resulting in morbidity of osteoarthritis.Ultrasonic applications in the medicine could be traced back to 1942. An Austrian Doctor Dussik applied it in the medical domain for the first time. With the in-depth study on ultrasonic function mechanism and improvement of relevant applied technology, nowadays ultrasonic has already been widely applied in clinic. Generally speaking, the frequency of Low Intensity Pulsed Ultrasound (LIPUS) is 1-3MHz with the intensity of being less than 100mW/cm2. It plays a role on improving cellular hypoxia and ischemia, increasing nutritional status of tissues, and enhancing cellular tissue regeneration ability through the cavitation effect, mechanical effect and heat effect. A great number of studies on the KOA animal model indicate that the treatment of LIPUS can relieve the cartilage injury degree of the experimental animals obviously. After animals with osteoarthritis are treated by LIPUS, MMP-13 expression in cartilage is reduced. The degradation velocity of type Ⅱ collagen is also reduced. The LIPUS can promote synthesis of protein polysaccharide and type Ⅱ collagen and develop a positive role on repairing articular cartilage.In recent years, due to features of safety, non-invasion, convenience and economy in LIPUS, it has been widely accepted by clinical doctors gradually and it is applied to the clinical treatment of KOA. For some patients in early and medium-term KOA, such physical therapy has already acquired the satisfactory curative effects.In the paper, by constructing a rabbit KOA model, influences of LIPUS on expression of Metalloproteinase inhibitor 2(TIMP-2) in rabbit KOA (Osteoarthritis) serum and matrix metalloproteinase-13(MMP-13) in articular chondrocytes were studied. Moreover, the LIPUS therapeutic apparatus was applied in clinic to do contrast treatment on patients with light and moderate KOA and further discuss the clinical applied values of LIPUS in curing KOA.Part 1 Effect of low intensity pulsed ultrasound on expression of TIMP-2 in serum and expression of mmp-13 in articular cartilage of rabbits with knee osteoarthritisObjective:To study the effect of low intensity pulsed ultrasound (LIPUS) on the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the serum and expression of matrix metallopeptidase 13 (MMP-13) in the articular cartilage cells of rabbits with knee osteoarthritis (OA).Methods:Inner patellar ligament defect method was used to establish the model of knee OA. Four weeks after the modeling, the arterial blood was drawn from the ear of each rabbit, while ELISA was employed to detect the expression of TIMP-2 in the serum. The chondrocytes were separated from animals in each group and then cultured in vitro. All rabbits were divided into control group, OA model group and OA+LIPUS group. Cells in the control and OA groups were not treated, while cells in the OA+LIPUS group were treated with LIPUS (1MHz,40mW/cm2,1 time/day). Cells were collected 7 d later and the RNA and total protein were extracted respectively. Real-time PCR and Western blotting were employed to analyze the expression of MMP-13 in chondrocytes at the mRNA and protein level, respectively.Results:1. The success rate of establishment of OA model was 83%.2. The results of ELISA showed that the content of TIMP-2 in the serum of animals with OA was 22.3%, lower than the one in the control group (P< 0.05).3. Compared with the normal control group, the expression of TIMP-2 in the OA model group was significantly increased, while the expression of MMP-13 was significantly increased (P< 0.05).4. After the stimulation of LIPUS, the expression of TIMP-2 and MMP-13 was close to the one in the normal control group.Conclusions:1. The inner patellar ligament defect method is a mature method to establish the rabbit OA model, with high success rate.2. The expression of serum TIMP-2 in the OA model group is significantly decreased.3. LIPUS can up-regulate TIMP-2 and down regulate MMP-13.Part 2 The Evaluation on Clinical Curative Effects of Low Intensity Pulsed Ultrasound in Curing Knee OsteoarthritisAbstractObjectives:The low intensity pulsed ultrasound (LIPUS) therapeutic apparatus will be applied to cure patients with KOA, for the sake of discuss the clinical applied values of LIPUS in curing KOA.Methods:120 patients with KOA who saw a doctor in the Department of Orthopedics of Liaocheng Third People’s Hospital from July 2014 to December 2015 were selected. According to random rules, these patients were divided into 60 patients of LIPUS treatment group and 60 patients of control group (without LIPUS treatment) and accepted 6-weeks treatment. VAS scoring, HSS scoring and SF-36 life quality scoring of patients in both groups before and after treatment were recorded. Based on X-ray staging criteria of KOA, respondents were divided into Phase Ⅰ、Phase Ⅱ and Phase Ⅲ. Their records of VAS scoring, HSS scoring and SF-36 life quality scoring before and after treatment were compared by staging, respectively. Moreover, the SF-36 life quality scoring was scored and settled as 8 dimensions. With the statistical analysis, clinical curative effects of LIPUS on curing patients with KOA in different stages were further evaluated.Results:1. The overall Vas scoring, HSS scoring and SF-36 scoring in the treatment group were superior to the control group after treatment. The scoring comparison between pre-treatment and post-treatment had a statistical difference, but the scoring difference in the control group before and after treatment was insignificant.2. According to the different X-ray stage, different pain degree, and different knee function grades were compared, the VAS scoring were significantly reduced after treatment in the LIPUS treatment group, with the obvious statistical significance(P< 0.05), but the difference was insignificant (P> 0.05) in the control group.3. In patients with the X-ray staging Phase Ⅰ to Ⅱ, pain degree mild to moderate, and the knee function rating were excellent and good, the HSS scoring comparison between post-treatment and pre-treatment had the statistical significance increase in the treatment group(P< 0.05). But in patients with X-ray staging Phase Ⅲ, severe pain and medium-term knee function, HSS scores did not change significantly after treatment (P> 0.05).4. The SF-36 total score and the scores of 8 dimension comparison after and before treatment showed that LIPUS treatment has the most curative effect in relieve body pain (BP), patients with X-ray staging Phase Ⅰ, Ⅱ and Ⅲ after treatment were significantly improved; Phase Ⅰ and Ⅱ patients have significant effect in most dimensions after LIPUS treatment, but in RP and RE dimensions effect is not obvious; Phase Ⅲ patients, except the BP dimension, other dimensions were not significantly improved.Conclusions:1. LIPUS treatment can significantly relieve the arthralgia symptoms of patients with KOA;2. LIPUS treatment of patients with early and medium-term; LIPUS treatment can significantly improve the knee function of KOA patients with X-ray staging Phase Ⅰ-Ⅱ; but for patients with Phase Ⅲ, severe pain and poor knee function the therapeutic effects is not good;3. LIPUS treatment can significantly improve the quality of life of patients with X-ray staging Phase Ⅰ-Ⅱ, and has obvious advantages in reducing the arthralgia of KOA patients.4. For patients with Phase Ⅲ, the knee joint function and quality of life were not significantly improved except for arthralgia relief after LIPUS treatment. |
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