[Caspase-1/-11 participates in LPS-induced sepsis-associated acute kidney injury by cleaving GSDMD].

The present study was aimed to investigate whether Gasdermin D (GSDMD)-mediated pyroptosis participated in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (AKI), and to explore the role of caspase-1 and caspase-11 pyroptosis pathways in this process. The mice were divided into four groups: wild type (WT), WT-LPS, GSDMD knockout (KO) and KO-LPS. The sepsis-associated AKI was induced by intraperitoneal injection of LPS (40 mg/kg). Blood samples were taken to determine the concentration of creatinine and urea nitrogen. The pathological changes of renal tissue were observed via HE staining. Western blot was used to investigate the expression of pyroptosis-associated proteins. The results showed that the concentrations of serum creatinine and urea nitrogen in the WT-LPS group were significantly increased, compared with those in the WT group (P < 0.01); whereas serum creatinine and urea nitrogen in the KO-LPS group were significantly decreased, compared with those in the WT-LPS group (P < 0.01). HE staining results showed that LPS-induced renal tubular dilatation was mitigated in GSDMD KO mice. Western blot results showed that LPS up-regulated the protein expression levels of interleukin-1ß (IL-1ß), GSDMD and GSDMD-N in WT mice. GSDMD KO significantly down-regulated the protein levels of IL-1ß, caspase-11, pro-caspase-1, caspase-1(p22) induced by LPS. These results suggest that GSDMD-mediated pyroptosis is involved in LPS-induced sepsis-associated AKI. Caspase-1 and caspase-11 may be involved in GSDMD cleavage.

The protective effects of electro-acupuncture in thoracic surgery on trauma stressed rats involve the rostral ventrolateral medulla and supraoptic nucleus.

The present study was designed to explore whether the rostral ventrolateral medulla (RVLM) and supraoptic nucleus (SON) were involved in the protective effects of electro-acupuncture (EA) in thoracic surgery on trauma-stressed rats. The rats were randomly divided into a non-stressed group (Control), surgical trauma-stressed group (Trauma), and Neiguan EA applied on the surgical trauma-stressed group (Trauma+EA-PC 6). RVLM neuron discharge was observed by using an in vivo electrophysiological method, and micro-dialysis combining high-performance liquid chromatography with fluorometric detection (HPLC-FD) was used to assess expression of amino acids in the RVLM. Immunohistochemical methods were used to assess c-Fos expression in SON neurons. The trauma of surgical stress was shown to dramatically increase the discharge frequency of RVLM neurons and promote the release of glutamate and taurine in the RVLM. The expression of c-Fos was also significantly increased in the SON of traumatized rats. EA application at Neiguan acupoints significantly suppressed trauma-induced increase of discharge frequency of the RVLM neurons, almost completely suppressed the trauma-induced increase of glutamate release but only very slightly reduced the trauma-enhanced taurine release, and inhibited the increase of c-Fos expression in these SON neurons of traumatized rats. These results indicate that Neiguan EA may improve cardiac function by modulating neurons in the RVLM and the SON in surgically traumatized rats. The taurine-mediated negative feedback may be involved in the protective effect of EA on cardiac function.