Study on Repairing Effect of Kangfuxin Liquid on Cartilage Defect of Knee Osteoarthritis Model Rabbits and Its Mechanisms / 中国药房

OBJECTIVE： To investigate the effects of Kangfuxin liquid on repairing cartilage defect model of knee osteoarthritis （KOA） in rabbits and its mechanism. METHODS： Totally 72 male New Zealand rabbits were selected and randomly divided into model control group and Kangfuxin low-dose， medium-dose， high-dose groups， with 18 rabbits in each group. A cartilage defect model of the medial femoral condyle of the right knee joint in rabbits was established by drilling after anesthesia surgery. Then the rabbits in each group were given medicine via articular cavity immediately. Kangfuxin low-dose， middle-dose and high-dose groups were given 20％， 40％， 80％ Kangfuxin liquid； model control group was given constant volume of normal saline consecutively， 0.2 mL/kg， once every 3 days. At 4th， 8th， 12th week after medication， the wound repair of cartilage defect in rabbits was observed. Immediately after medication and at 4th， 8th， 12th week after medication， repaired tissue of cartilage defect in rabbits was scored histologically with Wakitani scoring standard under light microscope. At 12th week after medication， pathological changes of repaired tissue of cartilage defect in rabbits were observed by Masson staining. The levels of NO， SOD and LPO in joint fluid and PYD in urine of rabbits were detected by ELISA. RESULTS： At 4th， 8th， 12th week after medication， compared with model control group， cartilage defects in rabbits were repaired well in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with immediately after medication and model control group at same time point， histomorphological score of repairing cartilage defect of knee joint in rabbits decreased significantly in Kangfuxin low-dose， medium-dose and high-dose groups （P＜0.05）. At 12th week after medication， compared with model control group， the histopathology degree of cartilage defect of knee joint in rabbits was significantly alleviated in Kangfuxin low-dose， medium-dose and high-dose groups. At 4th， 8th， 12th week after medication， compared with model control group， the levels of NO and LPO in joint fluid and PYD level in urine were decreased to different extent in Kangfuxin low-dose， medium-dose and high-dose groups， while SOD level was increased to different extent； at 12th week after medication， the difference of each index has statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： Kangangxin liquid can significantly repair cartilage defect of KOA cartilage defect model rabbits， the mechanism of which may be associated with increasing the expression of SOD and mediating NO-inhibited chondrocyte apoptosis.

Pyrin Domain (PYD)-containing Inflammasome in Innate Immunity

Inflammasome is a cytosolic multiprotein complex to activate caspase-1 leading to the subsequent processing of inactive pro-interleukin-1-beta (Pro-IL-1beta) into its active interleukin-1 beta (IL-1beta) in response to pathogen- or danger-associated molecular pattern. In recent years, a huge progress has been made to identify inflammasome component as a molecular platform to recruit and activate caspase-1. Nucleotide-binding oligomerization domain-like receptor (NLR) family proteins such as NLRP1, NLRP3 or interleukin-1beta-converting enzyme (ICE)-protease activating factor (IPAF) have been first characterized to form inflammasome complex to induce caspase-1 activation. More recently, non-NLR type, pyrin-domain (PYD)-containing proteins such as pyrin or absent in melanoma2 (AIM2) were also proposed to form caspase-1-activating inflammasome machinery with apoptosis-associated speck-like protein containing a CARD (ASC), an essential adaptor molecule. Inflammasome pathways were shown to be crucial for protecting host organisms against diverse pathogen infections, but accumulating evidences also suggest that excessive activation of inflammasome/caspase-1 might be related to the pathogenesis of inflammation-related diseases. Indeed, mutations in NLRP3 or pyrin are closely associated with autoinflammatory diseases such as familial Mediterranean fever (FMF) syndrome or Muckle-Wells syndrome (MWS), indicating that the regulation of caspase-1 activity by inflammasome is a central process in these hereditary inflammatory disorders. Here, recent advances on the molecular mechanism of caspase-1 activation by PYD-containing inflammasomes are summarized and discussed.

The Study of Urinary Hydroxypyridinium Crosslinks Concentrations in Patients with RA or OA , and Its Clinical Significance / 대한내과학회지

OBJECTIVES: To evaluate the urinary concentrations of hydroxyridinium crosslinks of collagen in patients with osteoarthritis(OA) or rheumatoid arthritis(RA), and to compare its clinical correlation with the classic indices of the disease activity of RA. METHODS: Concentrations of urinary pyridinoline (Pyd) and deoxypyridinoline(Dpd) were measured in urinary samples collected from 18 control patients, 35 patients with OA, 45 patients with RA by competitive enzyme immunoassay using microplate coated with monoclonal antibody. RESULTS: 1) Mean urinary concentrations of Pyd in OA patients were 33.5nmol/mmol creatinine, in RA patients were 50.0nmol/mmol creatinine which were higher than the values in controls (25.1 nmol/mmol creatinine). Also, mean concentrations of Dpd in OA patients were 9.2nmol/mmol creatinine, in RA patients were 10.1nmol/mmol creatinine which were higher than the values in controls(5.6nmol/mmol creatinine)(p<0.01). 2) Mean urinary concentration of Pyd was 50.0 nmol/mmol creatinine in RA patients, which was significantly higher than the values in OA(33.5 nnmol/mmol creatinine)(p<0.05), but the mean Dpd concentratians were not significantly different between the two groups. 3) The concentrations of urinary Pyd in RA patients was significantly correlated with the biologic markers indicating inflammatory activity such as ESR(r=0.68, p<0.001), CRP(r=0.72, p<0.001) and the number of tender joint(r=0.66, p<0.01) CONCLUSION: Urinary concentrations of Pyd and Dpd were significantly higher in OA and RA patients than in controls, Especially urinary Pyd concentrations were significantly increased in RA patients than in OA patients, and strongly correlated with disease activity index of rheumatoid arthritis. The mean Dpd concentration, bone specific analogue, in RA patients was not significantly different from that of OA patients and it was not correlated with disease activity index Thus measurement of urinary Pyd might provide a sensitive, noninvasive biochemical marker for studying activity of RA.