Extracts Of Oxytropis Kansuensis Induced Toxic Damage Of Rats And Protective Effects Of "Jifang E"

Locoweed is one of the most endangered poisonous weeds of the word, which widelydistributed in the natural grassland of northwest area in China. Livestocks get toxicated afteringesting it, which bring huge economic losses to the herdsmen every year, and restrict thesustainable development of hunsbandry industry in wstern China. Oxytropis Kansuensis is oneof the most distributed locoweed in China, the main toxic ingredient is swainsonine.Researches show that, swainsonine can strongly inhibit Golgi α-mannosidase Ⅱ（MAN2A1） and Lysosomalα-mannosidase （MAN2B1）, while the effects on theMAN2B1expression remains unknown. By now, there is no effective detoxicant againstswainonine.“Jifang E” is a preventive medicine of swainsonine, animal experiments haveshown that, it is effective to prevent the locoweed poisoning, while the mechanism remainsunknown. To investigate the toxic mechanism of swainsonine and the preventive effect of“Jifang E” from swainsoine, and its mechanism, this research chose SD rats as experimentanimal, used the alcohol ingredients of Oxytropis Kansuensis as the toxin, and “Jifang E” asthe antidote, to establish the chronic SW poisoning model of SD rats, and conductedexperiments as below:1. Establishing the chronic SW poisoning model of SD rats.60male SD rats wererandomLy distributed to3groups of20animals as Control Group, Challenge Group andProtecting Group. Rats in Control Group fed normal full feeding, while rats in ChallengeGroup and Protecting Group fed feedings containing9%alcohol ingredients of OxytropisKansuensis （0.0609‰SW）, and at the same time, rats in Protecting Group were gavagedsolution of “Jifang E”（20mg/kgBW） every other day, and the other rats were gavaged thesame dose of normal saline. On the120th day, rats in Challenge Group showed the typicalclinical signs of SW poisoning, while those in Protecting Group didn’t show the typical signs.2. The effects of Oxytropis Kansuensis and “Jifang E” on the serum biochemical indicesof SD Rats. On the30th,60th,90th and120th day, the blood samples of rats were collected todetect the biochemical indices. Results show that, Oxytropis Kansuensis can increase theactivity of ALT, AST, ALP, CRE and decrease the activity of TP, ALB, TBIL, LDH, Ca2+andBUN. And “Jifang E” can reduce the effects of SW towards the activity of AST, ALT, TP,ALB, CRE and Ca2+, show that “Jifang E” has protective effect on SD rats.3. The effects of Oxytropis Kansuensis and “Jifang E” on pathological changes of SD Rats. After dosing period, the rats were sacrificed and the tissues were collected to process theHE and PAS staining. Results show that, Oxytropis Kansuensis can induce the pathologicallesions of cerebrum, cerebellum, kidney, liver and spleen, and the most serious lesionsoccurred in liver, cerebellum and kidney. The main lesion was cellular vacuolation. And theanimals in the Protecting Group showed less serious lesions. And the PAS staining resultsshow that some of the vacuoles in heptocells, kidney and brain cells are filled with sugars.4. The effects of Oxytropis Kansuensis and “Jifang E” on the AMAN activity of SD Rats.After dosing period, the rats were sacrificed and the tissues were collected to make intohomogenates to detect the AMAN activity. Results show that, Oxytropis Kansuensis caninhibit the activity of AMAN, which was most obvious in liver, kidney and spleen, followedby cerebrum and cerebellum.“Jifang E” can reduce the effect of SW on AMAN in kidney andspleen, and other tissues was not significant.5. The effects of Oxytropis Kansuensis and “Jifang E” on the AMAN expression of SDRats. After dosing period, the rats were sacrificed and the tissues were collected to detect themRNA expression. Results show that, Oxytropis Kansuensis can downregulate the MAN2A1and MAN2B1mRNA expression in all the tissues, which is most obvious in liver, followedby kidney and spleen, and is least obvious in cerebrum and cerebellum.“Jifang E” can reducethe effect of SW on MAN2A1mRNA expression in cerebellum and spleen, and MAN2B1mRNA expression in in cerebrum and spleen, but the differences are not significant （P>0.05）. Oxytropis Kansuensis can downregulate the MAN2A1and MAN2B1proteinexpression in all the tissues, which is most obvious in kidney, followed by liver and spleen,and is least obvious in cerebrum and cerebellum.“Jifang E” can reduce the effect of SW onMAN2A1expression in liver, kidney and spleen, and MAN2B1expression in in cerebellum,live and spleen, but the differences of statistical analysis are not significant （P>0.05）.