Effects of Gegen Qinlian Decoction on NLRP3 inflammatome signaling pathway in liver of mice with type 2 diabetes mellitus / 国际中医中药杂志

ABSTRACT

Objective:To observe the effects of different doses of Gegen Qinlian Decoction on nucleotide oligomeric domain-like receptor protein 3 (NLRP3)/Caspase-1/IL1β inflammatory signaling pathway in liver of db/db mice with type 2 diabetes mellitus (T2DM).Methods:Totally 75 SPF male db/db mice were randomly divided into model group, metformin group (0.2 g/kg), Gegen Qinlian Decoction high-, medium-, and low-dosage groups (61.80, 30.90, 15.45 g/kg), with 15 mice in each group. Another 15 db/m male mice were selected as blank control group. Each administration group was given relevant medicine for gavage, while the blank group and model group were given 0.9% sodium chloride solution for gavage, once a day, for 12 weeks. The body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) contents of each group were measured after treatment. The mRNA expression levels of NLRP3, Caspase-1 and interleukin-1β (IL-1β) in liver were detected by real-time quantitative PCR. The expression levels of NLRP3, Caspase-1, IL-1β and IL-18 in liver tissues were detected by Western Blot. HE staining was used to observe the morphology of liver tissues.Results:Compared with model group, body weight, fasting blood glucose and HbA1c contents of mice in Gegen Qinlian Decoction high- and medium-dosage groups and metformin groups decreased ( P<0.05), the body weight and fasting blood glucose levels of mice in Gegen Qinlian Decoction low-dosage group decreased ( P<0.05); the mRNA levels of NLRP3 and IL-1β in liver tissues of all treatment groups decreased ( P<0.05), the mRNA level of Caspase-1 in liver tissue decreased in Gegen Qinlian Decoction high- and medium-dosage groups ( P<0.05); the expression of NLRP3, Caspase-1, and IL-18 in liver tissue of each treatment group decreased ( P<0.05), while the expression of IL-1β in Gegen Qinlian Decoction high- and medium-dosage groups and the metformin group decreased ( P<0.05); compared with the metformin group, the body weight and fasting blood glucose of mice in the Gegen Qinlian Decoction high-dosage decreased ( P<0.05), while the HbA1c levels in the Qinlian Decoction high- and medium-dosage decreased ( P<0.05); the expressions of NLRP3, Caspase-1 and IL-18 in liver tissues of Gegen Qinlian Decoction high-dosage group decreased ( P<0.05), the expression of IL-1β, NLRP3, Caspase-1, IL-1β, and IL-18 decreased ( P<0.05); HE staining showed that the pathological changes of liver tissue were reduced in all treatment groups. Conclusion:Gegen Qinlian Decoction may reduce blood sugar by inhibiting the activation of NLRP3/Caspase-1/IL-1β inflammatory signaling pathway in liver of db/db mice, thereby improving the inflammatory damage of T2DM.