Non-linear dependence of interstitial fluid pressure on joint cavity pressure and implications for interstitial resistance in rabbit knee

AIMS: Synovium retains lubricating fluid in the joint cavity. Synovial outflow resistance estimated as dPj/dQs (Pj, joint fluid pressure and Qs trans-synovial flow) is greater, however, than expected from interstitial glycosaminoglycan concentration. This study investigates whether subsynovial fluid pressure increases with intra-articular pressure, as this would reduce the estimated resistance estimate. METHODS: Interstitial fluid pressure (Pif) was measured as a function of distance from the joint cavity in knees of anaesthetized rabbits, using servo-null pressure-measuring micropipettes and using an external 'window'. Joint fluid pressure Pj was either endogenous (-2.4 +/- 0.4 cmH2O, mean +/- SEM) or held at approximately 4, 8 or 15.0 cmH2O by a continuous intra-articular saline infusion that matched the trans-synovial interstitial drainage rate. RESULTS: At endogenous Pj the peri-articular Pif was subatmospheric (-1.9 +/- 0.3 cmH2O, n = 19). At raised Pj the Pif values became positive. Gradient dPif /dx was approximately 20 times steeper across synovium than subsynovium. Pif close to the synovium-subsynovium border (Pif*) increased as a non-linear function of Pj to 1.4 +/- 0.2 cmH2O (n = 23) at Pj = 4.3 +/- 0.1 cmH2O : 2.3 +/- 0.2 cmH2O (n = 17) at Pj = 7.6 +/- 0.2 cmH2O: and 3.0 +/- 0.4 cmH2O (n = 26) at Pj = 15 +/- 0.2 cmH2O (P = 0.03, anova). CONCLUSIONS: Synovial resistivity is approximately 20x subsynovial resistivity. The increase in Pif*with Pj means that true synovial resistance d(Pj-Pif*)/dQs is overestimated 1.5x by dPj/dQs. This narrows but does not eliminate the gap between analysed glycosaminoglycan concentration, 4 mg ml(-1), and the net interstitial biopolymer concentration of 11.5 mg ml(-1) needed to generate the resistance.     

The relationship between interstitial fluid pressure and volume in rat trachea

A change of interstitial fluid volume (IFV) will normally change the interstitial fluid pressure (P_if) so as to counteract further fluid movement across the capillaries and changes in IFV. Contrary to this, several acute inflammatory reactions in the trachea are associated with increased negativity of P_if, which will interstitial fluid balance in the trachea, interstitial compliance (ΔIFV/ΔP_if) was measured in pentobarbital anaesthetized rats. IFV was measured as the plasma equivalent extravascular distribution space of [⁵¹Cr]EDTA. P_if was measured in the same animal with sharpened glass pipettes (diameter 3–6 μm) connected to a servocontrolled counterpressure system. In dehydration (30 mL saline i.v., n=10) interstitial compliance was 0.083 mL g dry wt^-1 mmHg^-1. Since control IFV was 1.046 mL g dry wt^-1 (n=10) the interstitial compliance is 8% of IFV per mmHg. In overhydration (30 mL NaCl, n=10) and dextran anaphylaxis (1 mL dextran 70, n=10) compliance remained the same for the first 15% increase in IFV and then increased several-fold since P_if did not increase more than 2 mmHg above control level. The increased negativity of P_if by -10 mmHg associated with acute inflammation will require a reduction of IFV by 80% when interstitial compliance is 8% per mmHg. A more likely explanation is therefore that structural rearrangements are responsible for the events leading to increased negativity of P_if in acute inflammation.     

Effects of lactoferrin on rat dermal interstitial fluid pressure (Pif) and in vitro endothelial barrier function

We recently demonstrated that intravenous (i.v.) injection of the iron‐binding protein lactoferrin (Lf) followed by antilactoferrin (aLf) antibodies or iron‐saturated Lf alone increased albumin extravasation in vivo in several tissues including skin. Increased driving pressure for blood‐tissue exchange or direct effects of Lf on the endothelial barrier are possible mechanisms. We therefore, firstly, measured interstitial fluid pressure (P_if) in dermis of rats given 1 mg Lf i.v. followed 30 min later by aLf or saline and circulatory arrest 1 or 5 min thereafter and compared with controls. Secondly, transmonolayer passage of Evans blue labelled albumin (EB‐albumin) was evaluated in porcine pulmonary artery endothelial cells exposed to iron‐free or iron‐saturated Lf (both 100 μg mL^–1) in the absence and presence of 0.5 mM hydrogen peroxide. P_if increased significantly at 11–30 min following Lf to +2.1 ± 0.3 and +1.7 ± 0.2 mmHg at 11–20 and 21–30 min, respectively, compared with +0.1 ± 0.2 mmHg before Lf (P < 0.05, n=25). Endothelial transmonolayer passage of EB‐albumin during 3 h was not affected by iron‐free or iron‐saturated Lf neither in the absence nor presence of hydrogen peroxide that increased passage 3.5 times compared with controls. In conclusion, Lf‐induced increase in albumin extravasation in rat skin is not explained by changes in P_if (because Lf raised P_if significantly) or direct effects of Lf on the endothelial barrier.     

Compliance of the interstitial space in rats I. Studies on hindlimb skeletal muscle

Interstitial compliance, defined as the ratio between changes in interstitial fluid volume (ΔIFV) and interstitial fluid pressure (ΔIFP), was determined for rat skeletal muscle. IFV was measured as the extravascular distribution space for ⁵¹Cr-EDTA, while sharpened micropipettes connected to a servo-controlled counterpressure system were used to measure IFP. The experimental protocol was designed to bring about acute (2–4 h) and chronic (24–28h) tissue over- and dehydration. During dehydration, the average compliance was 0.056 ml/g dry weight · mmHg, corresponding to 1.40 ml/100 g wet tissue mmHg, and was not significantly different in acute and chronic experiments. In hydration (acute and chronic), compliance increased several-fold when IFV increased. Even at greatly increased IFV, IFP did not rise more than 1 to 1.5 mmHg above control level. Since control IFV amounts to 10 ml/100 g wet tissue, IFV will decrease by 14% when IFP falls by 1 mmHg from this control level. Provided unchanged interstitial protein mass the dehydration will cause interstitial fluid colloid osmotic pressure to increase by somewhat more than 1 mmHg—from a control level of 9 mmHg. Furthermore, since IFP was not increased by more than 1 to 1.5 mmHg during hydration, an increase in IFP plays a minor role in edema-prevention compared to dilution and/or washout of interstitial proteins.     

A human knee joint model considering fluid pressure and fiber orientation in cartilages and menisci

Articular cartilages and menisci are generally considered to be elastic in the published human knee models, and thus the fluid-flow dependent response of the knee has not been explored using finite element analysis. In the present study, the fluid pressure and site-specific collagen fiber orientation in the cartilages and menisci were implemented into a finite element model of the knee using fibril-reinforced modeling previously proposed for articular cartilage. The geometry of the knee was obtained from magnetic resonance imaging of a healthy young male. The bones were considered to be elastic due to their greater stiffness compared to that of the cartilages and menisci. The displacements obtained for fast ramp compression were essentially same as those for instantaneous compression of equal magnitude with the fluid being trapped in the tissues, which was expected. However, a clearly different pattern of displacements was predicted by an elastic model using a greater Young's modulus and a Poisson's ratio for nearly incompressible material. The results indicated the influence of fluid pressure and fiber orientation on the deformation of articular cartilage in the knee. The fluid pressurization in the femoral cartilage was somehow affected by the site-specific fiber directions. The peak fluid pressure in the femoral condyles was reduced by three quarters when no fibril reinforcement was assumed. The present study indicates the necessity of implementing the fluid pressure and anisotropic fibril reinforcement in articular cartilage for a more accurate understanding of the mechanics of the knee.     

循经低流阻通道组织液压的初步观察

目的 测量循经低流阻通道与周围的组织液压,观察其差异及变化情况。方法 在麻醉的小型猪上,使用连续流阻测量仪测出低流阻点和非低流阻点,然后采取针中芯方法测量组织液压。结果 统计结果表明,小型猪胃经、肾经和任脉的低流阻通道平均压力均显著低于旁开的高流阻区域,其压力差分别为1.06、0.70、3.69 mmHg（1 mmHg=0．133 kPa）,总压力差为1.44 mmHg,压力梯度为1.44~2.88 mmHg/cm。在一些低流阻点上发现了与呼吸频率一致的压力波。结论 外周皮下组织中存在着指向经脉低流阻通道的压力差,可能构成组织液向经脉流动的动力。     

Impact of respiratory pattern on lung mechanics and interstitial proteoglycans in spontaneously breathing anaesthetized healthy rats

Aim: The aim of this study was to investigate the effect of different pattern of spontaneous breathing on the respiratory mechanics and on the integrity of the pulmonary extracellular matrix. Methods: Experiments were performed on adult healthy rats in which different spontaneously breathing pattern was elicited through administration of two commonly used anaesthetic mixtures: pentobarbital/urethane (P/U) and ketamine/medetomidine (K/M). The animals (five per group) were randomized and left to spontaneously breath for 10 min (P/U‐sham; K/M‐sham) or for 4 h (P/U‐4 h; K/M‐4 h), targeting the anaesthesia level to obtain a tidal volume of about 8 mL kg^?1 body wt. At the end of the experiment, lung matrix integrity was assessed through determination of the glycosaminoglycans (GAGs) content in the lung parenchyma. Results: Compared with K/M, anaesthesia with P/U cocktail induced: (1) a higher respiratory rate and minute ventilation attained with lower P_aCO₂; (2) a higher pressure‐time‐product and work of breathing per minute; (3) a lower static lung compliance; (4) an increased activation of lung tissue metalloproteases; and (5) greater extraction of pulmonary interstitial GAGs. Conclusions: This study suggests that the breathing pattern induced by the different anaesthetic regimen may damage the pulmonary interstitium even during spontaneous breathing at physiological tidal volumes.     

The interstitium conducts extrarenal storage of sodium and represents a third compartment essential for extracellular volume and blood pressure homeostasis

The role of salt in the pathogenesis of arterial hypertension is not well understood. According to the current understanding, the central mechanism for blood pressure (BP) regulation relies on classical studies linking BP and Na⁺ balance, placing the kidney at the very centre of long‐term BP regulation. To maintain BP homeostasis, the effective circulating fluid volume and thereby body Na⁺ content has to be maintained within very narrow limits. From recent work in humans and rats, the notion has emerged that Na⁺ could be stored somewhere in the body without commensurate water retention to buffer free extracellular Na⁺ and that previously unidentified extrarenal, tissue‐specific regulatory mechanisms are operative regulating the release and storage of Na⁺ from a kidney‐independent reservoir. Moreover, immune cells from the mononuclear phagocyte system not only function as local on‐site sensors of interstitial electrolyte concentration, but also, together with lymphatics, act as systemic regulators of body fluid volume and BP. These studies have established new and unexpected targets in studies of BP control and thus the pathophysiology of hypertension: the interstitium/extracellular matrix of the skin, its inherent interstitial fluid and the lymphatic vasculature forming a vessel network in the interstitium. Aspects of the interstitium in relation to Na⁺ balance and hypertension are the focus of this review. Taken together, observations of salt storage in the skin to buffer free extracellular Na⁺ and macrophage modulation of the extracellular matrix and lymphatics suggest that electrolyte homeostasis in the body cannot be achieved by renal excretion alone, but also relies on extrarenal regulatory mechanisms.     

Identification of a specific haptoglobin C‐terminal fragment in arthritic synovial fluid and its effect on interleukin‐6 expression

Haptoglobin (Hp), a major acute‐phase plasma protein, has been found in arthritic synovial fluid (SF). However, the function and structural modifications of Hp in arthritic SF are unknown. To investigate in vivo generation of modified Hp associated with inflammatory disease, we examined a new Hp isoform in SF from patients with rheumatoid arthritis (RA). Specific Hp fragments of 28 000 and 15 000 molecular weight were identified in SF of patients with RA, and the two polypeptides were presumed to be fragments of the Hp β‐chain (43 000 MW) produced by cleavage with plasmin. The 15 000 MW fragment, which is a C‐terminal region of Hp, was observed at higher frequency and levels in RA than in osteoarthritis. Plasmin activity was also higher in SF of RA patients. A recombinant 15 000 MW Hp fragment up‐regulated interlukin‐6 expression in monocytic cells. These findings indicate that the C‐terminal Hp fragment is generated by plasmin in local inflammatory environments and acts as an inflammatory mediator. They further suggest that a specific Hp fragment might be applied as a novel biomarker for the diagnosis and prognosis of inflammatory diseases such as RA.     

Distribution of interleukin‐10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation

Evidence exists that interleukin (IL)‐10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL‐20, IL‐24 and IL‐19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL‐20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL‐24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL‐19 serum levels were higher in HC and OA compared with PsA and RA patients; IL‐19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL‐19 serum levels after biological treatment. Therefore, IL‐19 seems to be involved mainly in the joint inflammation, whereas IL‐20 and IL‐24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies.     

Assessment of diffraction‐enhanced synchrotron imaging for cartilage degeneration of the human knee joint

Diffraction‐enhanced imaging (DEI) is a radiographic technology that harnesses the X‐ray refraction and scatter rejection properties that are not available with conventional radiography. Here, we test the efficacy of planar DEI to render images from which cartilage degeneration, characteristic of osteoarthritis, can be detected. DEI was carried out on human cadaveric intact knee joints at the X‐15 beamline at the National Synchrotron Light Source. The gross specimens and the DEI images were graded separately for levels of cartilage degeneration on six individual surfaces: anterior and posterior femoral and tibial on both medial and lateral sides. There was a significant correlation between the actual levels of cartilage degeneration and what was observed in their respective DEI images (P < 0.05) for all six articular surfaces. Some articular surfaces (patellar surfaces, in particular) could not be visualized because of overlap with superimposed bone. Sensitivity for the graded articular surfaces was 0.73 and specificity was 0.92 (Grade 0 being no lesion and Grades 1–6 being increasing gradations of lesions). Chondrocalcinosis was also observed in DEI images to a far greater extent compared with the conventional radiographs. DEI renders images that are significantly correlated with their actual gross morphology. Detection of lesions was better for more severe grades of degeneration than for partial focal lesions. Although some articular surfaces could not be visualized because of superimposed bone, we feel that DEI has potential for the diagnosis of cartilage lesions and chondrocalcinosis. Clin. Anat. 26:621–629, 2013. © 2012 Wiley Periodicals, Inc.     

Expression of caveolin‐3 in the fibroblast‐like type B synoviocytes in the rat temporomandibular joint

The present study revealed that the fibroblast‐like type B synoviocytes (covering the surface of the synovial membrane in the rat temporomandibular joint) had muscle‐specific caveolin‐3 protein in their caveolae. The existence of two kinds of type B synoviocytes (with and without caveolin‐3‐immunoreactions even in the synovial lining layer) might reflect the functional difference between them. Anat Rec, 2007. © 2007 Wiley‐Liss, Inc.     

A predominant Th1 polarization is present in synovial fluid of end-stage osteoarthritic knee joints: analysis of peripheral blood,synovial fluid and synovial membrane

Thorough understanding of the complex pathophysiology of osteoarthritis (OA) is necessary in order to open new avenues for treatment. The aim of this study was to characterize the CD4⁺ T cell population and evaluate their activation and polarization status in OA joints. Fifty-five patients with end-stage knee OA (Kellgren–Lawrence grades III–IV) who underwent surgery for total knee arthroplasty (TKA) were enrolled into this study. Matched samples of synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were analysed for CD3⁺CD4⁺CD8^– T cell subsets [T helper type 1 (Th1), Th2, Th17, regulatory T cells] and activation status (CD25, CD69, CD45RO, CD45RA, CD62L) by flow cytometry. Subset-specific cytokines were analysed by cytometric bead array (CBA). SM and SF samples showed a distinct infiltration pattern of CD4⁺ T cells. In comparison to PB, a higher amount of joint-derived T cells was polarized into CD3⁺CD4⁺CD8^– T cell subsets, with the most significant increase for proinflammatory Th1 cells in SF. CBA analysis revealed significantly increased immunomodulating cytokines [interferon (IFN)-γ, interleukin (IL)-2 and IL-10] in SF compared to PB. Whereas in PB only a small proportion of CD4⁺ T cells were activated, the majority of joint-derived CD4⁺ T cells can be characterized as activated effector memory cells (CD69⁺CD45RO⁺CD62L^–). End-stage OA knees are characterized by an increased CD4⁺ T cell polarization towards activated Th1 cells and cytokine secretion compared to PB. This local inflammation may contribute to disease aggravation and eventually perpetuate the disease process.     

Regulation of Non‐Infectious Lung Injury,Inflammation, and Repair by the Extracellular Matrix Glycosaminoglycan Hyaluronan

An important hallmark of tissue remodeling is the dynamic turnover of extracellular matrix (ECM). ECM performs a variety of functions in tissue repair including scaffold formation, modulation of fluid dynamics, and regulating cell behavior. During non‐infectious tissue injury ECM degradation products are generated that acquire signaling functions not attributable to the native precursor molecules. Hyaluronan (HA) is a non‐sulfated glycosaminoglycan which is produced in great abundance following tissue injury. It exists both in a soluble form and as side chains on proteoglycans. HA has critical roles in development as well as a variety of biological processes including wound healing, tumor growth and metastasis, and inflammation. HA fragments share structural similarities with pathogens and following tissue injury can be recognized by innate immune receptors. Elucidating the protean roles of HA in tissue injury, inflammation, and repair will generate new insights into mechanisms of diseases characterized by chronic inflammation and tissue remodeling. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

Differential effect of calcium phosphate and calcium pyrophosphate on binding of matrix metalloproteinases to fibrin: comparison to a fibrin-binding protease from inflammatory joint fluids

The ability of calcium phosphate (CaP) and calcium pyrophosphate (CaPPi) to mediate matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) binding to fibrin was evaluated. Substrate gel electrophoresis (gelatin zymography) revealed that CaP bound MMP-2 and MMP-9, forming a high molecular weight aggregate with lowered electrophoretic mobility. Formation of the CaP : MMP aggregate was necessary for fibrin binding. In contrast, CaPPi did not aggregate MMPs and did not promote uptake of MMPs into fibrin. Scatchard analysis (Ca/P ratio) revealed that CaPPi (1.96) was chemically similar to calcium pyrophosphate dihydrate (2.00) compared to amorphous CaP (1.50) or crystalline CaP, hydroxyapatite (1.66). MMP : CaP interaction appeared to be electrostatic in nature as high salt concentration (NaCl > 150 mm) reduced binding. In contrast, two non-ionic detergents (Brij-35 and Tween-20) did not prevent MMP : CaP binding. MMP : CaP interaction did not involve the C-terminal MMP region because the specific tissue inhibitor of metalloproteinases (TIMPs) also did not block MMP : CaP interaction and fibrin binding. Although MMP : CaP binding could be decreased with albumin, this effect appeared non-specific due to the high albumin concentration required. High albumin concentration could also partially dissociate preformed MMP : CaP complexes. Interestingly, type I and type IV collagen substantially increased MMP : fibrin-binding activity, whereas denatured collagen, gelatin, did not. Inflammatory joint fluid from five patients also demonstrated similar MMP fibrin-binding activity consistent with CaP mediation. The relevance of these findings to CaP and CaPPi in the pathogenesis of crystal arthropathies such as basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate crystal disease (CPPD) is discussed.     

Morphological and biochemical re-evaluation of the process of cavitation in the rat knee joint: cellular and cell strata alterations in the interzone

To assess the contribution of apoptosis to the mechanism of synovial joint cavitation, and to clarify morphological cellular changes during cavitation, we investigated the development of the rat knee joint by light and electron microscopy, TUNEL methods, and electrophoresis of DNA fragments. Although cavitation occurred within the interzone, which consists of 2 outer and a middle layer termed the intermediate zone, no morphological or biochemical signs of cell death, in particular apoptosis, were seen in the interzone at any embryonic stage. Microscopic and ultrastructural alterations affecting cell differentiation were clearly observed in the interzone, i.e. mesenchymal cells gradually showed elongation, cytoplasmic vacuolation and pyknosis in the intermediate zone where the elongated cells were arranged in parallel in some strata. Some of these cells were further flattened into spindle cells and the number of strata decreased to 2. The rest of the cells were incorporated secondarily into the outer layers, becoming chondroblasts. Collagen fibrils were arranged in a network structure in the outer layers, which obviously differed from the directional pattern parallel to the long axis of elongated cells in the intermediate zone. In addition, the density of collagen fibrils was higher in the outer layers than in the intermediate zone. During cavitation, the initial separation was detected between the elongated cells in the intermediate zone in paraffin sections at E16.5 and the spindle cells in epoxy sections at E18.5. The spindle cells lining the cavity, namely, the surfaces of the epiphysis and meniscus, finally became chondrocytes. The diminution of proteoglycans and collagen fibrils and the synthesis of hyaluronan in the extracellular matrix are now generally believed to be parts of the mechanism for cavitation based on the concept of ‘loss of cohesion’. The microscopic and ultrastructural alterations in the interzone seemed to reflect differences in the arrangement and density of collagen fibrils and the developmental condition of the extracellular matrix between layers. Also it did not seem likely that these alterations inhibit the synthesis of hyaluronan at the presumptive joint line because this synthesis takes place at the plasma membrane. Separation between spindle cells should therefore represent the mechanism for developmentally programmed cavitation. Reorganization of the extracellular matrix is probably necessary for the cellular metamorphoses in the interzone involved in the process of cavitation.     

Expression of TIM‐3 on CD4+ and CD8+ T cells in the peripheral blood and synovial fluid of rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by a chronic inflammatory process that targets the synovial lining of diarthrodial joints. TIM‐3 plays a key role in the negative regulation of the immune response. In this study, we investigated the expression of TIM‐3 on CD4+ and CD8+ T cells from systemic (peripheral blood) and local (synovial fluid) perspectives of RA. Level of TIM‐3+ cells from peripheral blood and synovial fluid of patients as well as peripheral blood of healthy controls was measured by flow cytometry. Results showed that TIM‐3 expression was significantly increased in both CD4+ and CD8+ T cells in the peripheral blood of RA (p < 0.001 and p < 0.001, respectively). Furthermore, patients revealed even higher expression of TIM‐3 in CD4+ and CD8+ T cells in synovial fluid than in peripheral blood. When comparing TIM‐3 level with the severity of RA, we identified that the percentage of TIM‐3 on both peripheral CD4+ and peripheral CD8+ T cells was negatively correlated with disease activity score 28 (DAS28) of the patients. Similarly, TIM‐3 on synovial fluid CD4+ and CD8+ T cells also revealed inverse correlation with DAS28 of the cases. Our data demonstrate a negative correlation between TIM‐3 and the disease progression of RA.     

长距离跑步大鼠膝关节滑膜基质金属蛋白酶的表达

背景：很多研究表明基质金属蛋白酶 1,3,9和13 对关节软骨的退变存在影响,但是针对关节滑膜进行的专项研究相对较少。 目的：观察长距离跑步运动对基质金属蛋白酶1,3, 9以及基质金属蛋白酶13在滑膜上的表达的影响。 方法：Wistar雄性大鼠15只随机分为3组：对照组、平板组和上坡组。对照组普通笼养;平板组每天在平板0°的水平面跑步机上以1 km/h,运动1 h,持续45 d;上坡组先在平板0°跑步机上以1 km/h,运动1 h,持续15 d,然后在上坡+20°的跑步机上每天以1 km/h,运动1 h,持续30 d。造成不同程度的膝关节滑膜损伤模型,造模成功后取双后肢膝关节,进行石蜡包埋,矢状面整体切片,而后进行苏木精-伊红和免疫组织化学染色,观察并分析实验结果。 结果与结论：长距离跑步运动后,平板组和上坡组的滑膜组织中基质金属蛋白酶1的表达都比对照组增高    (P < 0.05),但平板组和上坡组之间差异无显著性意义(P > 0.05);而3组基质金属蛋白酶3的表达并无明显变化(P > 0.05);基质金属蛋白酶9和基质金属蛋白酶13在滑膜组织中的表达呈梯度递增状态(P < 0.05),对照组表达最低,平板组有所升高,上坡组的表达最高。说明长距离跑步运动可通过改变基质金属蛋白酶的表达而影响大鼠膝关节滑膜组织的正常生理结构。