The Protective Effect of SLNP on Hepatic Fibrosis Induced by Thioacetamide in Rats.

INTRODUCTION: The incidence of non-alcoholic fatty liver disease (NAFLD) has increased in recent years. Hepatic fibrosis (HF) is an important step in the progression of NAFLD to cirrhosis and even carcinoma and is also recognized as a possible reversal phase. AIMS: We previously found that the aqueous extract of Sedum Lineare Thunb. has hepatoprotective effects. This study investigated the hepatoprotective effect and mechanism of the Sedum Lineare Thunb. n-butanol phase (SLNP) on HF in rats. METHODS: Animals were intraperitoneally injected with thioacetamide solution twice a week for 8 weeks to prepare an HF model and were administered the corresponding drugs or an equal volume of normal saline by intragastric administration once a day for 8 weeks. Liver function, hydroxyproline and malondialdehyde (MDA) content, superoxide dismutase (SOD), Na+-K+-ATPase, and Ca2+-Mg2+-ATPase were analyzed using colorimetric methods. Moreover, mRNA expression and protein levels in the liver tissue were detected via quantitative polymerase chain reaction and western blotting, respectively. RESULTS: The results showed that SLNP could effectively improve the liver function of rats with HF and significantly reduce the content of hydroxyproline; the mRNA expression and protein levels of alpha-smooth muscle actin (α-SMA), collagen I, III, and IV, transforming growth factor beta 1 (TGF-ß1), Smad2/3, and Smad4 were also significantly reduced. Simultaneously, SLNP significantly increased the activities of SOD, Na+-K+- ATPase, and Ca2+-Mg2+-ATPase in the rat liver tissues, whereas it reduced the levels of MDA and SOD in the serum and liver tissues. CONCLUSION: This study revealed that SLNP elicits an anti-fibrotic effect by inhibiting oxidative stress and stellate cell activation, thereby reducing the formation and deposition of the extracellular matrix. The TGF-ß1/Smads signaling pathway may be involved in this process.

Genistein-3'-sodium sulfonate Attenuates Neuroinflammation in Stroke Rats by Down-Regulating Microglial M1 Polarization through α7nAChR-NF-κB Signaling Pathway.

Microglial M1 depolarization mediated prolonged inflammation contributing to brain injury in ischemic stroke. Our previous study revealed that Genistein-3'-sodium sulfonate (GSS) exerted neuroprotective effects in ischemic stroke. This study aimed to explore whether GSS protected against brain injury in ischemic stroke by regulating microglial M1 depolarization and its underlying mechanisms. We established transient middle cerebral artery occlusion and reperfusion (tMCAO) model in rats and used lipopolysaccharide (LPS)-stimulated BV2 microglial cells as in vitro model. Our results showed that GSS treatment significantly reduced the brain infarcted volume and improved the neurological function in tMCAO rats. Meanwhile, GSS treatment also dramatically reduced microglia M1 depolarization and IL-1ß level, reversed α7nAChR expression, and inhibited the activation of NF-κB signaling in the ischemic penumbra brain regions. These effects of GSS were further verified in LPS-induced M1 depolarization of BV2 cells. Furthermore, pretreatment of α7nAChR inhibitor (α-BTX) significantly restrained the neuroprotective effect of GSS treatment in tMCAO rats. α-BTX also blunted the regulating effects of GSS on neuroinflammation, M1 depolarization and NF-κB signaling activation. This study demonstrates that GSS protects against brain injury in ischemic stroke by reducing microglia M1 depolarization to suppress neuroinflammation in peri-infarcted brain regions through upregulating α7nAChR and thereby inhibition of NF-κB signaling. Our findings uncover a potential molecular mechanism for GSS treatment in ischemic stroke.

[Expression of acid-sensing ion channels in neurons of trapezoid body and lateral paragigantocellular nuclei in rat brain, and effects of intermittent hypoxia on their expression].

OBJECTIVE: To investigate the expression of three acid-sensing ion channel (ASIC) subtypes termed as ASIC1b, ASIC2a, and ASIC3 in the neurons of trapezoid body and lateral paragigantocellular nucleus of rat brainstem, and the effects of intermittent hypoxia on their expression. METHODS: The intermittent hypoxic rat model was established, of which the blood gas analysis was tested after 12 days. The immunohistochemistry SABC method was performed to test the expression of ASIC1b, ASIC2a, and ASIC3 in neurons of trapezoid body and lateral paragigantocellular nucleus in the control (O2) and intermittent hypoxic (IH) groups of rats. RESULTS: The ASIC1b-, ASIC2a- and ASIC3-positive immunoreactive neurons all could be observed in the nucleus of trapezoid body and lateral paragigantocellular nucleus. The intermittent hypoxia group, the numerical density of ASIC1b-positive immunoreactive neurons (cell/mm3) decreased in the nucleus of trapezoid body (P<0.05), but did not significantly change in the lateral paragigantocellular nucleus (P>0.05), the grey level did not significantly change in both the nucleus of trapezoid body and lateral paragigantocellular nucleus (P>0.05); the numerical density of ASIC2a-positive immunoreactive neurons (cell/mm3) did not significantly change in the nucleus of trapezoid body and lateral paragigantocellular nucleus (P>0.05), the grey level in the nucleus of trapezoid body increased (P<0.05) while it did not significantly change in the lateral paragigantocellular nucleus (P>0.05); the numerical density of ASIC3-positive immunoreactive neurons (cell/mm3) decreased in the lateral paragigantocellular nucleus (P<0.05), but it did not significantly change in the nucleus of trapezoid body (P>0.05), the grey level did not significantly change in the nucleus of trapezoid body and lateral paragigantocellular nucleus (P>0.05). CONCLUSION: The ASIC1b, ASIC2a, and ASIC3 exist in the neurons of trapezoid body and lateral paragigantocellular nucleus in the rat brainstem under normal condition, and their expressions in the two nuclei are different to intermittent hypoxia, which means that the roles of subtype of ASICs in different area may be different in the respiratory effects induced by hypoxia.