Kratak sadr`aj: Eksperimenti vezani za regeneraciju jetre posle parcijalne hepatektomije pokazali su da TNF-a, HGF i TGF-b1 kao i drugi citokini igraju va`ne uloge u razli~itim faza ma regeneracije jetre, me|utim, uticaj arterijalizacije port ne vene (APV) na ekspresiju ovih citokina tokom regene racije jetre nije jasan. Sprague Dawley pacovi nasumi~no su podeljeni u APV grupu i kontrolne grupe, a krv za detekciju ALT uzeta je pomo}u automatskog biohemijskog analiza tora. Ekspresije TNF-a, HGF i TGF-b1 u tkivima jetre detektovane su kvantitativnom RT-PCR. Nivoi ALT u obe grupe u po~etnom periodu posle operacije bili su zna~ajno vi{i nego pre hirur{kog za hvata i postepeno su se normalizovali posle 7 dana od operacije. Posle 12 h i 24 h od zahvata, ekspresija TNF-a u APV grupi bila je zna~ajno vi{a nego u kontrolnoj grupi (P<0,05), ali posle 7 dana od operacije nije uo~ena zna~ajna razlika izme|u dve grupe. Ekspresija HGF u APV grupi posle 12 h bila je sli~na onoj u kontrolnoj grupi, ali je posle 24 h bila zna~ajno vi{a nego u kontrolnoj grupi (P<0,05). Posle 24 h, ekspresija TGF-b1 u APV grupi bila je zna~ajno ni`a nego u kontrolnoj grupi (P<0,05), ali posle 48 h od operacije izme|u dve grupe nije otkrivena zna~ajna razlika. Pozitivan uticaj na arterija li zaciju portne vene u ranim fazama regeneracije jetre bio je povezan s promenama u ekspresijama TNF-a, HGF i TGF-b1. Summary: Experiments on liver regeneration after partial hepatectomy have shown that TNF-a, HGF and TGF-b1 and other cytokines play important roles in the different stages of liver regeneration, however, the effect of portal vein arteria liz ation (PVA) on the expressions of these cytokines during liver regeneration is not clear. Sprague Dawley rats were randomly divided into the PVA group and control groups, and blood was collected for the detection of ALT using an automatic bio chemical analyzer. The expressions of TNF-a, HGF and TGF-b1 in liver tissues were detected by quan titative RT-PCR. The ALT levels in both groups in the early period after surgery were significantly higher than those before operation, and gradually returned to normal at 7 days after surgery. At 12 h and 24 h after operation, the TNF-a expres sion in the PVA group was significantly higher than that in the control group (P<0.05), but no significant dif fe rence at 7 days after sur gery was observed between the two groups. At 12 h, the HGF expression in the PVA group was similar to that in the con trol group, but significantly higher than in the control group at 24 h (P<0.05). At 24 h, the TGF-b1 expres sion in the PVA group was sig nificantly lower than that in the control group (P <0.05), but no significant difference was found at 48 h after surgery between the two groups. The promo tive effects on the portal vein arterialization at the early stage of liver rege neration were associated with the changes in the expressions of TNF-a, HGF and TGF-b1.
Background: Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). Objective: To assess the antinociceptive effect of TSN IIA on CIBP. Study Design: A randomized, double-blind, controlled animal trial was performed. Setting: University lab in China. Methods: A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. Results: TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1β, TNF-α, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. Limitations: Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. Conclusions: Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. Key words: Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain, breakthrough pain
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