[Influence of Moxibustion on TLR 4-MyD 88-NF-KB Signal Transduction Pathway of Synovial Tissue in Rheumatoid Arthritis Rats].

OBJECTIVE: To observe the effect of moxibustion intervention on the expression of toll-like receptor-4 (TLR 4), myeloid differentiation factor 88(MyD 88), and nuclear factor kappa B p 65 (NF-κB p 65) genes of knee-joint synovial cells in rheumatoid arthritis (RA) rats, so as to explore its molecular mechanism underlying improving RA. METHODS: Forty SD rats were randomly divided into normal control, RA model, moxibustion and medication groups (n = 10). The RA model was duplicated by raising the rats in a windy, cold and wet environment, followed by injecting Freund's complete adjuvant (0. 15 mL) into the rat's foot. Moxibustion was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36) for 20 min, once daily for 15 days. Rats of the medication group were treated by intragastric administration of tripterygium wilfordii (8. 75 mL/kg), once daily for 15 days. Pathological changes of the synovial tissues were detected by H. E. stain, the contents of serum TNF-α and IL-1 detected by radioimmunoassay, and the expression levels of TLR 4 mRNA, MyD 88 mRNA and TRAF-6 mRNA of synovial tissue were analyzed by real time-PCR, and the NF-κB p 65 immunoactivity was assayed by immunohistochemistry. RESULTS: In comparison with the normal control group, the synovial tissue of the knee-joint was impaired remarkably and infiltrated by numerous inflammatory cells, and the synovial surface got thickening because of hyperplasia in the model group. Following moxibustion and medication, these situations such as synovial infiltration of inflammatory, synovial cell proliferation were alleviated. The serum TNF-α and IL-1 contents and synovial TLR 4 mRNA, MyD 88 mRNA, TRAF-6 mRNA and NF-κB p 65 expression levels were remarkably higher in the model group than in the control group(P<0. 01). After moxibustion and medication, the contents of serum TNF-α and IL-1, the expression levels of TLR 4 mRNA, MyD 88 mRNA, TRAF-6 mRNA and NF-κB p 65 were significantly down-regulated(P<0. 01, P<0. 05). CONCLUSION: Moxibustion intervention can improve pathological changes of the knee-joint synovial membrane tissue in RA rats, which may be related with its effect in inhibiting abnormal activation of TLR 4-MyD 88-NF-κB pathway in synovial tissue.

[Effects of Moxibustion on Expression of STAT 1, SOCS mRNA in Synovium of Rats with Rheumatoid Arthritis].

OBJECTIVE: To observe the effect of moxibustion on mRNA expression of signal transducers and activators of transcription 1 (STAT 1), suppressors of cytokine signaling (SOCS) in synovium of rheumatoid arthritis (RA) rats, and to investigate its mechanism for relieving RA. METHODS: 40 Wistar rats were equally and randomly divided into control, model, moxibustion, acupuncture and infrared groups (n = 8 in each group). RA model was developed by putting rats in windy, cold and damp room and injection of Freund's complete adjuvant. Bilateral "Shenshu" (BL 23) were stimulated by the respective means for 20 min in duration, once every other day, ten times in total. The swelling degree of voix pedis (perimeter) of rats was measured. The contents of serum interleukin-1 (IL-1) and interleukin-2(IL-2) were detected by radioimmunoassay, and expression of STAT 1, SOCS mRNA in synovium were assessed by RT-PCR. RESULTS: Rats in model group had acute and severe swelling of voix pedis, together with the increase of serum IL-1 content and decrease of IL-2 content, and down-regulation of mRNA expression of both STAT 1 and SOCS in synovium(all P<0. 01). All three modalities of treatment alleviated the swelling and reversed the relevant changes(P<0. 05, P<0. 01) , however, moxibustion produced greater effects than acupuncture or infrared in elevating IL-2 content and up-regulating mRNA expression of both STAT 1 and SOCS. CONCLUSION: Moxibustion achieves the effects of anti-inflammation and joint swelling reduction of RA via decrease of IL-1, increase of IL-2 in serum and up-regulation of STAT 1, SOCS mRNA expression in synovium.

[Effect of moxibustion on ultrastructure of synovial cells in rheumatoid arthritis rats].

OBJECTIVE: To observe the influence of moxibustion of "Shenshu"(BL 23) and "Zusanli" (ST 36) on the microstructure of synovial cells in the knee-joint in rheumatoidarthritis (RA) rats so as to study its underlying mechanism in anti-inflammatory immune effect. METHODS: A total of 120 Wistar rats were randomized into normal control, model, acupuncture, moxibustion, CO2-laser and medication groups (n = 20/group). RA model was duplicated by raising the rats in a windy (electro-fan blowing), cold [(6 +/- 2) degrees] and wet (80%-90%) environment for 12 h/d and 20 days, followed by injecting Freund's complete adjuvant (0.15 mL) into the rat's ankle. Moxibustion or acupuncture or CO2 laser (10.6 microm) irradiation was applied to "Shenshu" (BL 23) and "Zusanli" (ST 36) for 20 min, once daily for 15 days. Intragastric perfusion of Leigongteng (Tripterygium Wilfordii Hook.f.) was given to medication group, 8 mg/kg, once daily for 15 days. The thoracic gland index [weight of the thoracic gland (mg)/ body weight (g) x 100%] and spleen index [weight of the spleen (mg)/body weight (g) x 100%] were calculated after killing the rats under anesthesia. The ultrastructure of synovial cells of the knee-joint was observed by using transmission electron microscopy. RESULTS: In comparison with the normal control group, the thoracic gland index in the model group was decreased significantly (P < 0.01), while the spleen index of the model group increased considerably (P < 0.05). In comparison with the model group, the thoracic gland indexes in the acupuncture, moxibustion, CO-laser and medication groups were increased significantly (P < 0.05, P < 0.01), whereas the spleen indexes in the four groups decreased evidently (P < 0.05). No significant differences were found among the acupuncture, moxibustion, CO2-laser and medication groups in up-regulating the thoracic gland index and down-regulating the spleen index (P > 0.05). After modeling, the synoviocytes of the knee-joint were impaired remarkably, exhibiting incomplete cellular membrane, some prolapsed organelles, marginalized stained granules in the cellular nucleus, vague nuclear membrane, enlarged rough endoplasmic reticulum, reduction in the number of mitochondria with vacuolization degeneration and multiple lysosomes. But, the pathological changes of the ultrastructure of most synoviocytes in the acupuncture, moxibustion, CO2-laser and medication groups were relatively milder. CONCLUSION: Moxibustion can protect the immune organs (thoracic gland and spleen) from injury and improve pathological changes of the ultrastructure of local synoviocytes in RA rats.

Predictive value of three surgical scoring systems for estimation of life expectancy in patients with extradural spinal metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the predictive values of Tokuhashi score, revised Tokuhashi score and Tomita score systems for life expectancy and treatment options in patients with spinal metastasis.</p><p><b>METHODS</b>From February 1996 to January 2009, spinal operations in 104 cases with spinal metastasis were performed in our hospital. There were 65 males and 39 females, with an average of 53.4 years (median 52.5 years). To calculate AUC (area under the curve) values of Receiver Operating Characteristic (ROC) curves of three scores, and to analyze the accuracy of prediction of life expectancy. To compare the actual survival time with the expected survival time of the three scores by Kaplan-Meier method. Spearman correlation analysis was performed between the survival time and three scoring systems.</p><p><b>RESULTS</b>All cases were followed-up with an average duration of 10.9 months, and 77 patients died. AUC analysis of ROC curves showed that the difference of the accuracy of the three scores was not significant. AUC in all groups of Tokuhashi Score was low, with a poor diagnostic accuracy. In the "died within 3 months" and "died within 6 months" groups of revised Tokuhashi score, the accuracy was low, while high in the other two groups. The AUC values of Tomita score in "died within 6 months" and "died within 24 months" were high, with a great diagnostic accuracy while the other two groups were low with a low diagnostic accuracy. Kaplan-Meier survival curve analysis showed that the actual survival time in all three scores was not entirely consistent with the expected survival time. Tokuhashi score and revised score were positively correlated with the survival time while that of Tomita score was negative.</p><p><b>CONCLUSION</b>All the three prognosis scores in patients with spinal metastasis were closely related with survival time. The combination of Tokuhashi score and Tomita score may be applied to better predict postoperative survival prognosis and guide the surgical options for patients with spinal metastasis.</p>