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复杂脂质 SPPCT-800 可减轻脂多糖诱导的急性呼吸窘迫综合征(ARDS)模型小鼠的肺损伤,改善肺功能,降低促炎细胞因子水平。

The complex lipid, SPPCT-800, reduces lung damage, improves pulmonary function and decreases pro-inflammatory cytokines in the murine LPS-induced acute respiratory distress syndrome (ARDS) model.

机构信息

SignPath Pharma, Inc, New York, NY, USA.

IPS Therapeutique, Sherbrooke, Quebec, Canada.

出版信息

Pharm Biol. 2022 Dec;60(1):1255-1263. doi: 10.1080/13880209.2022.2087689.

DOI:10.1080/13880209.2022.2087689
PMID:35786152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9255205/
Abstract

CONTEXT

Acute respiratory distress syndrome (ARDS) is a highly fatal, inflammatory condition of lungs with multiple causes. There is no adequate treatment.

OBJECTIVE

Using the murine LPS-induced ARDS model, we investigate SPPCT-800 (a complex lipid) as treatment for ARDS.

MATERIALS AND METHODS

C57B16/N mice received 50 μg of O111:B4 lipopolysaccharide (LPS). SPPCT-800 was given as either: (1) 20 or 200 mg/kg dose 3 h after LPS; (2) 200 mg/kg (prophylactically) 30 min before LPS; or (3) eight 200 mg/kg treatments over 72 h. Controls received saline installations.

RESULTS

At 48 and 72 h, SpO was 94% and 90% in controls compared to 97% and 94% in treated animals. Expiration times, at 24 and 48 h, were 160 and 137 msec for controls, but 139 and 107 msec with SPPCT-800. In BALF (24 h), cell counts were 4.7 × 10 (controls) and 2.9 × 10 (treated); protein levels were 1.5 mg (controls) and 0.4 mg (treated); and IL-6 was 942 ± 194 pg/mL (controls) versus 850 ± 212 pg/mL (treated) [at 72 h, 4664 ± 2591 pg/mL (controls) versus 276 ± 151 pg/mL (treated)]. Weight losses, at 48 and 72 h, were 20% and 18% (controls), but 14% and 8% (treated). Lung injury scores, at 24 and 72 h, were 1.4 and 3.0 (controls) and 0.3 and 2.2 (treated).

DISCUSSION AND CONCLUSIONS

SPPCT-800 was effective in reducing manifestations of ARDS. SPPCT-800 should be further investigated as therapy for ARDS, especially in longer duration or higher cumulative dose studies.

摘要

背景

急性呼吸窘迫综合征(ARDS)是一种由多种原因引起的肺部炎症性疾病,病死率极高。目前尚无有效的治疗方法。

目的

使用小鼠脂多糖诱导的 ARDS 模型,我们研究 SPPCT-800(一种复合脂质)作为 ARDS 的治疗药物。

材料和方法

C57B16/N 小鼠给予 50μg O111:B4 脂多糖(LPS)。SPPCT-800 以以下三种方式给药:(1)LPS 后 3 小时给予 20 或 200mg/kg 剂量;(2)LPS 前 30 分钟给予 200mg/kg(预防)剂量;或(3)72 小时内给予 8 次 200mg/kg 剂量。对照组给予生理盐水。

结果

在 48 和 72 小时时,对照组的 SpO2 为 94%和 90%,而治疗组的 SpO2 为 97%和 94%。在呼气时间方面,对照组在 24 和 48 小时时分别为 160 和 137 毫秒,而 SPPCT-800 组则分别为 139 和 107 毫秒。在 BALF(24 小时)中,细胞计数分别为 4.7×10(对照组)和 2.9×10(治疗组);蛋白水平分别为 1.5mg(对照组)和 0.4mg(治疗组);IL-6 分别为 942±194pg/mL(对照组)和 850±212pg/mL(治疗组)[72 小时时,4664±2591pg/mL(对照组)和 276±151pg/mL(治疗组)]。对照组在 48 和 72 小时时的体重减轻分别为 20%和 18%,而治疗组分别为 14%和 8%。对照组在 24 和 72 小时时的肺损伤评分分别为 1.4 和 3.0,而治疗组分别为 0.3 和 2.2。

讨论与结论

SPPCT-800 可有效减轻 ARDS 的表现。SPPCT-800 应作为 ARDS 的治疗药物进一步研究,特别是在更长时间或更高累积剂量的研究中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/24624e8fddfe/IPHB_A_2087689_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/8587c8c4e2fc/IPHB_A_2087689_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/628170bba501/IPHB_A_2087689_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/45b9f0c52049/IPHB_A_2087689_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/24624e8fddfe/IPHB_A_2087689_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/8587c8c4e2fc/IPHB_A_2087689_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/628170bba501/IPHB_A_2087689_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/45b9f0c52049/IPHB_A_2087689_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d9d/9255205/24624e8fddfe/IPHB_A_2087689_F0004_C.jpg

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