[Effect of dexmedetomidine on expression of tight junction protein ZO-1 in kidney tissue of rats with acute kidney injury induced by sepsis].

OBJECTIVE: To observe the effect of dexmedetomidine (DEX) on the expression of tight junction protein ZO-1 in kidney tissues of rats with acute kidney injury (AKI) induced by sepsis. METHODS: Sixty healthy male Sprague-Dawley rats were selected and divided into four groups: sham operation group (Sham group), DEX + Sham group, cecal ligation and puncture (CLP) group and DEX + CLP group according to a random number table, with 15 rats in each group. Each group was then divided into 3 subgroups at 6, 12, and 24 hours after the operation, with 5 rats in each subgroup. Modified CLP was used to establish a sepsis model. In Sham group and DEX + Sham group, only laparotomy and abdominal closure were performed. Each group was given pretreatment 1 hour before modeling. DEX + Sham group and DEX + CLP group were pumped into DEX at a rate of 5 µg×kg-1×h-1 through the caudal vein; Sham group and CLP group were pumped with the equal amount of normal saline through the caudal vein. Rats in each group were sacrificed at 6, 12, and 24 hours after operation to obtain kidney tissue. After hematoxylin-eosin (HE) staining, the pathological changes were observed under a light microscope, and the pathological score of renal injury was calculated. The positive expression level of ZO-1 in kidney tissue was detected by immunohistochemistry. RESULTS: The pathological changes of rat kidney tissue could be seen at 6 hours after CLP. With the prolongation of postoperative time, the degree of renal injury showed a tendency to aggravate, with 24 hours being more significant. Semi-quantitative analysis showed that compared with the Sham group, the CLP group had significantly higher renal injury pathology scores at each time point (1.98±0.37 vs. 0.36±0.25 at 6 hours, 2.62±0.34 vs. 0.39±0.18 at 12 hours, 3.52±0.34 vs. 0.42±0.20 at 24 hours,all P < 0.01); the positive expression level of ZO-1 in kidney tissue was significantly reduced [percentage of positive area: (3.17±0.74)% vs. (10.83±0.83)% at 6 hours, (2.56±0.76)% vs. (9.02±0.88)% at 12 hours, (1.75±0.66)% vs. (8.25±0.94)% at 24 hours, all P < 0.01]. Compared with the CLP group, the pathological score of renal injury in the DEX + CLP group was significantly reduced at each time point (0.66±0.27 vs. 1.98±0.37 at 6 hours, 1.34±0.26 vs. 2.62±0.34 at 12 hours, 2.08±0.38 vs. 3.52±0.34 at 24 hours, all P < 0.01); the positive expression level of ZO-1 in kidney tissue was significantly increased [percentage of positive area: (8.58±0.86)% vs. (3.17±0.74)% at 6 hours, (7.44±1.05)% vs. (2.56±0.76)% at 12 hours, (6.60±0.87)% vs. (1.75±0.66)% at 24 hours, all P < 0.01]. There was no significant difference in renal injury pathology score and ZO-1 positive expression between the DEX+Sham group and the Sham group. CONCLUSIONS: DEX may reduce sepsis-induced AKI in rats by up-regulating the expression of tight junction protein ZO-1 in kidney tissue.

TEG in the monitoring of coagulation changes in patients with sepsis and the clinical significance.

Application values of thromboelastography (TEG) in dynamic monitoring of coagulation parameters of sepsis patients were investigated. Eighty-one patients with sepsis who were admitted to the ICU department of the General Hospital of Ningxia Medical University from April 1, 2015 to December 31, 2015 were collected. Clinical data of the patients were collected. Data were compared using 5 grouping methods: i) the 81 patients were divided into the sepsis group (n=45) and sepsis shock group (n=36); ii) patients were divided into two groups: group A (APACHE II score ≤13, n=51); group B (APACHE II score >13, n=30); iii) according to Disseminated Intravascular Coagulation Diagnosis Integral System (CDSS), patients were divided into non-disseminated intravascular coagulation (DIC) group (CDSS <7 points) and DIC group (CDSS ≥7 points); TEG indexes were compared between the two groups; iv) correlation between TEG indexes and Sequential Organ Failure Assessment (SOFA) scores was analyzed; v) patients were divided into survival group and non-survival group and correlations between TEG indicators and prognosis were analyzed. At 6 h after ICU entry, compared with sepsis group, R value and K time were significantly increased, LY30 was also increased, while MA value, coagulation index (CI), and α angle were significantly decreased in the septic shock group (P<0.05). At 6 h after ICU entry, compared with sepsis group, R value and K time were significantly increased, while MA value, CI, and α angle were significantly decreased in the septic shock group (P<0.05). Compared with the non-DIC group, the DIC group had prolonged K time, decreased α angle, increased R value, and decreased CI and MA value (P<0.05). With increase of SOFA scores, R value and K value increased significantly, and α angle, MA value, and CI decreased significantly (P<0.05). According to TEG, platelet function and fibrinogen function of DIC patients were significantly reduced, and the body showed hypocoagulability.

Colquhounia Root Tablet Protects Rat Pulmonary Microvascular Endothelial Cells against TNF-α-Induced Injury by Upregulating the Expression of Tight Junction Proteins Claudin-5 and ZO-1.

BACKGROUND: There are currently limited effective pharmacotherapy agents for acute lung injury (ALI). Inflammatory response in the lungs is the main pathophysiological process of ALI. Our preliminary data have shown that colquhounia root tablet (CRT), a natural herbal medicine, alleviates the pulmonary inflammatory responses and edema in a rat model with oleic acid-induced ALI. However, the potential molecular action mechanisms underlining its protective effects against ALI are poorly understood. This study aimed to investigate the effects and mechanism of CRT in rat pulmonary microvascular endothelial cells (PMEC) with TNF-α-induced injury. METHODS: PMECs were divided into 6 groups: normal control, TNF-α (10 ng/mL TNF-α), Dex (1×10-6 M Dex + 10 ng/mL TNF-α), CRT high (1000 ng/mL CRT + 10 ng/mL TNF-α), CRT medium (500 ng/mL CRT + 10 ng/mL TNF-α), and CRT low group (250 ng/mL CRT + 10 ng/mL TNF-α). Cell proliferation and apoptosis were detected by MTT assay and flow cytometry. Cell micromorphology was observed under transmission electron microscope. The localization and expression of tight junction proteins Claudin-5 and ZO-1 were analyzed by immunofluorescence staining and Western blot, respectively. RESULTS: TNF-a had successfully induced an acute endothelial cell injury model. Dex and CRT treatments had significantly stimulated the growth and reduced the apoptosis of PMECs (all p < 0.05 or 0.01) and alleviated the TNF-α-induced cell injury. The expression of Claudin-5 and ZO-1 in Dex and all 3 CRT groups was markedly increased compared with TNF-a group (all p < 0.05 or 0.01). CONCLUSION: CRT effectively protects PMECs from TNF-α-induced injury, which might be mediated via stabilizing the structure of tight junction. CRT might be a promising, effective, and safe therapeutic agent for the treatment of ALI.