ABSTRACT
Objective:To investigate the expression of platelet receptor CD62P in septic rats and the anti-inflammatory effect of ticagrelor and its protective effect on myocardial injury in septic rats.Methods:Thirty-two male SD rats were randomly(random number) divided into 4 groups: sham group, cecal ligation and puncture group(CLP), low dose group: the dose of 10 mg/kg, high dose group: the dose was 50 mg/kg, 8 rats in each group. The rats in the sham operation group were only treated with abdominal switch and cecum stripping, and the rats in the sepsis group, the low dose group and the high dose group were treated with CLP method to establish the sepsis model. The rats in the ticagrelor administration group were treated with ticagrelor at a dose of 10 mg/kg and 50mg/kg by gavage, respectively. The sham operation group and the sepsis group were treated with normal saline (1 mL/kg) by gavage. The rats were administrated twice by gavage 12 hours before and 12 hours after surgery. Blood samples were collected from the abdominal aorta 24 hours after modeling and then pathological specimens were collected. The expression of platelet surface receptor CD62P was detected by flow cytometry. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The levels of myocardial injury markers including CKMB and LDH were detected. The levels of transaminase, creatinine and white blood cell were detected. HE staining was used to observe the pathological morphology of myocardial tissue. Cardiomyocyte apoptosis was observed by TUNEL assay.Results:① Compared with sham group, the expression of CD62P in CLP group significantly increased ( P<0.01). Compared with the CLP group, the expression levels of CD62P in the two treatment groups significantly decreased, and the HD group was more significant ( P <0.01).②ELISA results showed that compared with sham group, the level of IL-6 in CLP group was significantly increased ( P<0.05). Compared with the CLP group, the HD group significantly decreased ( P< 0.05). There was no significant decrease in IL-6 level in the LD group. The level of TNF-α in CLP group was significantly higher than that in sham group ( P< 0.01). ③ Compared with sham group, the expression levels of CKMB and LDH in CLP group and two ticagrelor intervention groups significantly increased ( P <0.01). Compared with the CLP group, CKMB and LDH in the treatment group significantly decreased ( P <0.05), and the HD group decreased more significantly ( P<0.01). ④ Compared with sham group, WBC, ALT, CR values in CLP group significantly increased, while after the intervention with ticagrelor, WBC, ALT, CR values in rats significantly decreased ( P <0.05), and the difference significantly related to the dose. ⑤ The pathological results showed that the morphology of myocardial cells in sham group was normal. The CLP group most myocardial cell injury. LD and HD group the CLP group obviously reduce myocardial cell injury.⑥ Tunel staining showed that compared with a small number of positive cells in Sham group, a large number of positive cells were stained in CLP group. The apoptosis of myocardial cells in LD and HD groups significantly reduced compared with CLP group. Conclusions:Sepsis activates platelets and stimulates the overexpression of CD62P, which induces excessive activation of inflammatory response, induces apoptosis and damage of cardiomyocytes, and leads to septic myocardial injury. The cardioprotective effect of ticagrelor may be related to the inhibition of the reduction of CD62p expression after platelet activation, and the expression level of CD62p has a dose-dependent relationship with ticagrelor.
ABSTRACT
With the extensive applications of nuclear energy in the military, scientific research, and medical fields, radiological medicine has developed into a significant discipline. So far, studies of radiology have been conducted mostly using cell and animal models, both of which have limitations. Organoids, as 3D in vitro culture systems derived from tissue stem cells, have filled the gap left by these conventional models. They have been widely applied in review, disease research, drug development, and cancer modeling since their structures, functions, and genetic characteristics are akin to those of primary tissues. This review presents the applications of organoid models of various organ types in radiotherapy, as well as the limitations and prospects of organoids.