ABSTRACT
ObjectiveTo explore the mechanism of Fuzi Lizhongwan alleviating the damage of chemotherapy-induced peripheral neuropathy （CIPN） mice caused by cisplatin based on mitogen-activated protein kinase （MAPK） signaling pathway. MethodA total of 40 female KM mice were randomized into blank group （distilled water， ig）， model group （distilled water， ig）， Fuzi Lizhongwan group （3.5 g·kg-1， ig）， and aspirin group （0.026 g·kg-1， ig）. Cisplatin （3 mg·kg-1， ip， 5 days） was used to induce CIPN in mice. Administration began while modeling and lasted 12 days. The general conditions and behaviors of mice were observed. After the last administration， samples were collected. Pathological changes of the soles were observed based on hematoxylin-eosin （HE） staining. Biochemical assay was employed to determine the levels of serum superoxide dismutase （SOD）， hydrogen peroxide （H2O2）， malondialdehyde （MDA）， and nitric oxide （NO）， enzyme-linked immunosorbent assay （ELISA） the content of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and glutathione peroxidase-3 （GPX-3） in kidney tissue， and Western blotting the expression of extracellular signal-regulated kinase1/2 （ERK1/2）， phosphorylated-ERK1/2 （p-ERK1/2）， p38 MAPK， and phosphorylated-p38 MAPK （p-p38 MAPK） in kidney tissue. ResultCompared with the blank group， model group demonstrated obvious pathological damage on the soles， hyperkeratosis of the epidermis with a basketweave pattern， atrophy of stratum spinosum， reduction of cells， and intracellular edema. Compared with the model group， Fuzi Lizhongwan significantly alleviated the pathological damage of the skin tissue of the soles. The model group showed lower body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， higher content of H2O2， MDA， and NO （P<0.01）， and higher expression of IL-6， IL-1β， and TNF-α （P<0.01） than the blank group. Fuzi Lizhongwan group demonstrated higher body weight， mechanical pain threshold， thermal pain threshold （P<0.01）， and SOD activity （P<0.05）， lower content of H2O2， MDA， and NO （P<0.05）， and lower expression of IL-6， IL-1β， and TNF-α （P<0.01） than the model group. The expression of ERK1/2， p-ERK1/2， p38 MAPK， and p-p38 MAPK increased significantly （P<0.01） in the model group compared with that in the blank group， while the expression decreased significantly （P<0.01） in the Fuzi Lizhongwan group compared with that in the model group. ConclusionFuzi Lizhongwan can relieve the neurological injury of cisplatin-induced CIPN mice and increase the pain threshold of mice， possibly by regulating the MAPK signaling pathway and inhibiting inflammatory response and oxidative stress.
ABSTRACT
<b>Objective::To detect the expression levels of leptin (LEP), acety-coenzyme A carboxylase(ACC) and malonyl-CoA (MCA)-related proteins and their genes in rat tissues, in order to explore the mechanism and dose-effect relationship of modified Wendantang in alleviating lipid metabolism disorder in female nutritional obese rats. <b>Method::Totally 50 SD female rats were randomly divided into 5 groups according to body weight, namely the normal control group, the model control group, and high, medium and low-dose modified Wendantang groups (18.2, 9.1, 4.55 g·kg<sup>-1</sup>). Except the normal control group, the remaining rats were fed with " common feed + high fat emulsion + carbonated beverage" to establish the model of nutritional obesity, and then continuously given drugs by gavage for 5 weeks. After the last drug administration to animals in each group, the rats were anaesthetized to collect materials. The serum LEP, and liver and gastrocnemius ACC levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Quantitative real-time fluorescence polymerase chain reaction (Real-time PCR) was used to detect the expressions of LEP, MCA and ACC2 mRNA in the hypothalamus and liver tissues of each group. <b>Result::Compared with the normal control group, the body weight and fat index of the model control group increased significantly (<italic>P</italic><0.05). Compared with the model control group, the medium-dose modified Wendantang group could significantly down-regulate the expressions of LEP, MCA mRNA in rat hypothalamus (<italic>P</italic><0.01). The low-dose group can significantly down-regulate the expression levels of serum LEP, hypothalamus tissue LEP, MCA mRNA and liver tissue ACC2 mRNA (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the high-dose modified Wendantang group and the middle-dose modified Wendantang group had the best effect in down-regulating the expressions of LEP and MCA mRNA in the hypothalamus of rats, which were followed by the low-dose group (<italic>P</italic><0.05, <italic>P</italic><0.01). <b>Conclusion::The mechanism of modified Wendantang against nutritional obesity in female rats is related to the intervention of LEP resistance and the decrease of the expression level of ACC2 mRNA in liver tissue and MCA mRNA in hypothalamus tissue. The middle and low-dose groups have a better effect.
ABSTRACT
Objective:To observe the effect of Shaoyao Gancaotang and its disassembled prescriptions on the expressions of transient receptor potential vanilloid 3 (TRPV3) and transient receptor potential vanilloid 4 (TRPV4) in myocardium and hypothalamus of rats in the ultra-high temperature environment, in order to explore the mechanism of Shaoyao Gancaotang and its disassembled prescriptions against the high temperature. Method:Seventy five male SPF-grade SD rats were randomly divided into 5 groups according to their body weight, namely normal control group, high temperature normal control group, Shaoyao Gancaotang group (2.16 g·kg-1), single Paeoniae Radix Alba(PRA) group (1.08 g·kg-1) and single Glycyrrhizae Radix et Rhizoma(GRR) group (1.08 g·kg-1). Except normal control group, the remaining groups were fed in artificial climate boxes for 13 days. The normal control group and the high temperature normal control group were given the same volume of pure water. Western blot and quantitative real-time fluorescence polymerase chain reaction(Real-time PCR) were used to determine expressions of TRPV3, TRPV4 protein and mRNA in myocardium and hypothalamus of each group. Result:Compared with the normothermic control group, the expressions of TRPV3 protein, TRPV4 mRNA, TRPV3 protein and TRPV3 mRNA in the myocardium of the hyperthermic control group were significantly higher than those of the normal control group (PPPConclusion:TRPV3, TRPV4 channels in rat myocardium and hypothalamus were activated in the high temperature environment. The anti-hyperthermic mechanism of Shaoyao Gancaotang and its disassembled prescriptions was related to the regulation of TRPV3, TRPV4 channel protein and mRNA expressions in rat myocardium and hypothalamus.