ABSTRACT
Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.
ABSTRACT
OBJECTIVE:To investigate the effects of calcitriol on related indicators in patients with chronic renal failure (CRF). METHODS:114 patients with CRF were randomly divided into observation group(57 cases)and control group(57 cas-es). Control group was given high-quality low-protein and low phosphorus diet,if necessary,phosphate binders,Calcium D3 tablet and other conventional treatment;observation group was additionally given 0.25 μg Calcitriol soft capsule,once a day. The treat-ment course for both groups was 8 weeks. Serum levels of inflammatory factors,alkaline phosphatase,hemoglobin,erythrocyte, serum creatinine and urea nitrogen levels and adverse reactions in 2 groups before and after treatment were observed. RESULTS:Before treatment,there were no significant differences in the serum levels of inflammatory factors,alkaline phosphatase,hemoglobin, erythrocyte,senum creatininine and ureanitrogen between 2 groups(P>0.05). After treatment,serum inflammatory factors,alkaline phosphatase,serum creatinine and urea nitrogen levels in 2 groups were significantly shorter than before,and observation group was lower than control group,the differences were statistically significant (P0.05). And there was no obvious adverse reac-tions between 2 groups during treatment. CONCLUSIONS:Based on the conventional treatment,calcitriol can reduce the levels of serum inflammatory factors and improve micro-inflammatory state and renal function in patients with CRF.
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Objective To investigate effect of different doses of rosuvastatin on brachial artery endothelium-dependent vasodilation and carotid intima-media thickness in patients with coronary heart disease.Methods 92 patients with coronary heart disease in our hospital were admitted and divided into four groups according to randomly digital method, including 23 cases in control group were treated with lipid nitrate, antiplatelet aggregation, anticoagulant, lowering blood sugar, blood pressure control and other of conventional therapy;23 cases in group A, on the basis of conventional therapy, were treated with rosuvastatin 5 mg/d, orally, once daily;23 cases in group B were treated with rosuvastatin 10 mg/d, orally, once daily based on the conventional therapy;23 cases in group C were treated with rosuvastatin 20 mg/d, orally, once daily based on conventional treatment, each group was treated for 8 weeks.Brachial artery endothelium-dependent vasodilation (FMD) and carotid intima-media thickness (IMT) of patients before and after treatment were collected by color ultrasonic doppler, while observed lipid levels changes of 4 groups.Results Control group was treated for eight weeks, FMD, ITM, blood lipid levels and each index values were not significantly changed, the difference was not statistically significant;After treatment, total cholesterol ( TC) , low-density lipoprotein cholesterol C ( LDL-C) of A, B, C groups were significantly better than that before treatment, the difference was statistically significant (P<0.05), and decrease amplitude with dose of rosuvastatin increased became grearer, but the total cholesterol (TC), high density lipoprotein cholesterol C( HDL-C) there was no significant difference compared with before treatment; Compared with before treatment, ITM of A, B, C groups decreased, and the difference was statistically significant (P<0.05), decrease amplitude with dose of rosuvastatin increased became greater.Conclusion Rosuvastatin can significantly improve brachial artery endothelium-dependent vasodilation and carotid intima-media thickness in patients with coronary heart disease, and there is a clear dose-response relationship, which may be associated with rosuvastatin decrease total cholesterol and low-density lipoprotein cholesterol C in patients with coronary heart disease.It has guide significance to clinical.