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小檗碱通过抑制 TLR4/NF-κB 信号通路减轻大鼠脓毒症性心肌病。

Berberine attenuates septic cardiomyopathy by inhibiting TLR4/NF-κB signalling in rats.

机构信息

Department of Ultrasonography, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou, China.

Department of Cardiology, The Second Affiliated Hospital, University of South, Hengyang, China.

出版信息

Pharm Biol. 2021 Dec;59(1):121-128. doi: 10.1080/13880209.2021.1877736.

Abstract

CONTEXT

Berberine (Ber) can increase the survival rate of septic mice and inhibit inflammation, but whether it has a protective effect on septic cardiomyopathy (SCM) is unclear.

OBJECTIVE

To investigate whether Ber ameliorates SCM in a rat model and its potential mechanism.

MATERIALS AND METHODS

Male SD rats were randomly divided into three groups: control (Con,  = 6) (DD HO, 2 mL/100 g, ig, qd × 3 d, then saline, 10 mg/kg, ip); sepsis [LPS (lipopolysaccharide),  = 18] (LPS 10 mg/kg instead of saline, ip); and berberine intervention (Ber,  = 18) (Ber, 50 mg/kg instead of DD HO, ig, qd × 3 d, LPS instead of saline, ip). Hemodynamics, HE staining, ELISA and western blot were performed at 6, 24, and 48 h after intraperitoneal injection of LPS to evaluate the effect of berberine in septic rats.

RESULT

Berberine could recover myocardial injury by partially increased ± dp/dt max (1151, 445 mmHg/s) and LVEDP levels (1.49 mmHg) with LPS-induced rats, as well as an ameliorated increase of cTnT (217.53 pg/mL) in the Ber group compared with that in the LPS group (at 24 h). In addition, HE staining results showed that berberine attenuated the myocardial cell swelling induced by LPS. In contrast to the LPS group, the up-regulation of TLR4, p65 TNF-α, and IL-1β were attenuated in the Ber group.

DISCUSSION AND CONCLUSIONS

Berberine showed a protective effect on septic cardiomyopathy rats possibly through inhibiting the activation of TLR4/NF-κB signalling pathway. Whether it improves SCM through other mechanisms is our ongoing research.

摘要

背景

小檗碱(Ber)可以提高脓毒症小鼠的存活率并抑制炎症,但它是否对脓毒性心肌病(SCM)有保护作用尚不清楚。

目的

探讨 Ber 是否改善脓毒症大鼠模型中的 SCM 及其潜在机制。

材料和方法

雄性 SD 大鼠随机分为三组:对照组(Con,n=6)(DD HO,2ml/100g,ig,qd×3d,然后用生理盐水,10mg/kg,ip);脓毒症组(LPS,n=18)(用 LPS 代替生理盐水,ip);小檗碱干预组(Ber,n=18)(用 Ber 代替 DD HO,ig,qd×3d,用 LPS 代替生理盐水,ip)。在 LPS 腹腔注射后 6、24 和 48h 进行血流动力学、HE 染色、ELISA 和 Western blot 检测,以评估 Ber 在脓毒症大鼠中的作用。

结果

Ber 可部分恢复 LPS 诱导的大鼠心肌损伤,增加±dp/dt max(1151、445mmHg/s)和 LVEDP 水平(1.49mmHg),并降低 cTnT(217.53pg/mL)水平,与 LPS 组相比,Ber 组的 cTnT 水平升高。此外,HE 染色结果表明,Ber 减轻了 LPS 引起的心肌细胞肿胀。与 LPS 组相比,Ber 组 TLR4、p65 TNF-α和 IL-1β的上调受到抑制。

讨论与结论

Ber 对脓毒性心肌病大鼠具有保护作用,可能通过抑制 TLR4/NF-κB 信号通路的激活。它是否通过其他机制改善 SCM 是我们正在进行的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7069/8871679/e225221edeb3/IPHB_A_1877736_F0001_B.jpg

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